The clinical evidence for hyperbaric oxygen therapy in long COVID is real but mixed, and the split runs on dose. One sham-controlled randomized trial from Tel Aviv (73 patients, 40 sessions at 2.0 ATA) found moderate improvements in cognition (d=0.50), psychiatric symptoms (d=0.64), pain (d=0.74), and fatigue (d=0.52), and a 232-patient registry saw 65% improve. But two 2025 randomized trials using only 10 sessions found no benefit, and 15% of registry patients got worse. The honest reading: 40-session protocols show promise, short courses do not, and the evidence remains limited to a few centers.
- Sham-controlled: control patients sit in the same chamber at near-normal pressure on air, so neither they nor the assessors know who received real treatment.
- Cohen’s d: a standardized effect size. Roughly, 0.2 is small, 0.5 is moderate, 0.8 is large.
- Global longitudinal strain (GLS): an echocardiography measure of heart muscle function that detects damage before ejection fraction drops.
Long COVID affects an estimated 10 to 30% of people infected with SARS-CoV-2, and no drug reliably treats its underlying biology. That gap is why hyperbaric oxygen therapy has drawn attention. This page walks through every controlled trial, the registry data, the dose-response pattern that separates the positive studies from the negative ones, and the honest limitations, so the decision rests on what the research actually shows. For the patient-facing overview, see our guide to HBOT for lingering COVID-19 symptoms.
What did the landmark Tel Aviv RCT find?
The Tel Aviv trial (Zilberman-Itskovich et al., 2022) randomized 73 long COVID patients to 40 hyperbaric sessions at 2.0 ATA or sham, double-blind. The HBOT group showed moderate, statistically significant gains in global cognition (d=0.50), attention, executive function, energy (d=0.52), psychiatric symptoms (d=0.64), and pain interference (d=0.74), with matching increases in brain perfusion on MRI. It remains the only sham-controlled RCT to show benefit.
The trial, published in Scientific Reports, ran at the Sagol Center for Hyperbaric Medicine and Research.1 Patients had documented post-COVID symptoms lasting at least three months. The treatment arm received 40 sessions of 90 minutes at 2.0 ATA on 100% oxygen, five days a week for eight weeks. The sham arm sat through 40 sessions in the same chamber at near-ambient pressure on room air, engineered so patients could not tell the groups apart. Brain MRI with perfusion sequences was taken before and after.
| Outcome | Effect size (Cohen’s d) | p-value |
|---|---|---|
| Global cognitive function | 0.495 | 0.038 |
| Attention | 0.477 | 0.04 |
| Executive function | 0.463 | 0.05 |
| Energy and fatigue | 0.522 | 0.029 |
| Sleep quality | 0.48 | 0.042 |
| Psychiatric symptoms | 0.636 | 0.008 |
| Pain interference | 0.737 | 0.001 |
Effect sizes and p-values from Zilberman-Itskovich et al., Scientific Reports, 2022.1
HBOT improved global cognitive function (d=0.50), psychiatric symptoms (d=0.64), pain interference (d=0.74), and energy and fatigue (d=0.52) compared to sham in 73 long COVID patients, with brain MRI confirming increased perfusion in frontal and insular regions.
Zilberman-Itskovich et al., Scientific Reports, 2022
The imaging is what separates this trial from symptom-only reports. MRI perfusion showed statistically significant increases in cerebral blood flow across frontal and temporal regions in the HBOT group only, including the supramarginal gyrus, right insula, and multiple frontal areas. A companion analysis by Catalogna and colleagues (2022) reported changes in functional and structural brain connectivity in the same cohort.2 These are regions tied to the cognitive domains that improved, which links the reported gains to a measurable biological change rather than subjective reporting alone. The cognitive side is covered in depth in our HBOT for long COVID brain fog article.
Do the improvements last?
Follow-up evidence suggests the gains persist, but it comes from one small extension of the original cohort. Hadanny and colleagues (2024) reassessed 31 of the Tel Aviv patients an average of 486 days after treatment ended and found quality-of-life improvements held at a similar magnitude to the short-term results, with sleep gains maintained at effect sizes of 0.47 to 0.79.
This longitudinal follow-up, also in Scientific Reports, is the only published data beyond three months.4 Its durability finding is consistent with the proposed mechanism: hyperbaric oxygen is thought to drive angiogenesis (new blood vessel formation) and neuroplasticity, structural changes that would not reverse the moment treatment stops (Thom, 2011; Efrati, 2013).1719 The same durable, structural pattern was documented when the Efrati group applied HBOT to post-concussion syndrome and to stroke (Boussi-Gross, 2013; Efrati, 2013).2019 The trade-off is obvious: 31 patients from a single center is thin evidence on which to promise lasting benefit.
What does the real-world registry data show?
The largest real-world dataset (van Berkel et al., 2025) tracked 232 long COVID patients treated at clinical HBOT facilities and found 65% achieved a clinically relevant improvement in quality of life at three months, while 15% clinically deteriorated. This is the most honest picture available: most patients improved, cognitive symptoms responded best, but a real minority got worse.
The prospective registry, published in Scientific Reports, defined a clinically relevant response as a 10-point or larger change in the SF-36 mental or physical component score.10 Unlike a controlled trial with strict entry criteria, a registry captures the full spread of real patients, which is why it surfaces both the responders and the 15% who worsened. That worsening rate is the single most important number for informed consent, and it does not appear in the controlled trials. An earlier uncontrolled pilot by Robbins and colleagues (2021) first reported improvements in fatigue and cognition in 10 patients, but without a control group it cannot separate treatment from natural recovery or placebo.6 Cost and coverage for a full course are covered in our HBOT long COVID cost and insurance guide.
Why do 10-session trials fail when 40-session trials succeed?
Dose is the variable that best explains the conflicting results. The only positive sham-controlled RCT used 40 sessions. The two randomized trials that found nothing (HOT-LoCO and the Belgian D’hoore trial, both 2025) used only 10 sessions. The biology fits: angiogenesis and neuroplasticity need weeks of repeated exposure, so a two-week course may end before structural change occurs, and dosage analyses in related neurological conditions point to the same pressure-and-repetition window (Harch, 2022).22
HOT-LoCO (Kjellberg et al., 2025) randomized 80 patients at Karolinska to 10 sessions at 2.4 ATA or sham and found no difference on its primary physical-function endpoints (p=0.87 and p=0.57).11 Its earlier interim report had already confirmed the protocol was safe, so the null result reflects efficacy, not dropout.12 The D’hoore trial randomized 101 patients into four arms (100% oxygen at 2.5 ATA, 40% oxygen at 2.5 ATA, and two normobaric conditions), 10 sessions each, and again found no meaningful separation from placebo.13 The comprehensive 2026 review by Zoccali and colleagues singled out session count as the critical variable separating positive from negative trials.14 The dosing question is explored further in our how many HBOT sessions for long COVID article.
Positive vs Null Long COVID HBOT Trials
| Study | n | Pressure | Sessions | Result | Source |
|---|---|---|---|---|---|
| Zilberman-Itskovich 2022 (sham RCT) | 73 | 2.0 ATA | 40 | Positive (cognition, mood, pain, fatigue) | Sci Rep |
| Leitman 2023 (cardiac sub-study) | 60 | 2.0 ATA | 40 | Positive (GLS improved) | Sci Rep |
| Hadanny 2024 (follow-up) | 31 | 2.0 ATA | 40 | Positive, durable at ~486 days | Sci Rep |
| Robbins 2021 (pilot, uncontrolled) | 10 | 2.4 ATA | 10 | Positive but no control group | Clin Med |
| van Berkel 2025 (registry) | 232 | Clinical | Varied | Mixed: 65% improved, 15% worse | Sci Rep |
| HOT-LoCO 2025 (sham RCT) | 80 | 2.4 ATA | 10 | Null (primary endpoints) | BMJ Open |
| D’hoore 2025 (placebo RCT) | 101 | 2.5 ATA | 10 | Null | Diving Hyperb Med |
Read top to bottom, the pattern is hard to miss. Every positive controlled result used 40 sessions at 2.0 ATA. Every null result used 10. The registry sits in between, reflecting mixed real-world protocols and patients. This is the dose-response story that any patient or clinician should weigh before starting.
What do the systematic reviews conclude?
The systematic reviews are cautiously positive but consistent in their caveats. They find HBOT tends to improve cognition, fatigue, and quality of life with few serious side effects, while flagging small samples, heterogeneous protocols, and the concentration of positive data in a few centers. None treat the question as settled.
Wu and colleagues (2024) reviewed 10 clinical studies in Life and concluded most showed gains in quality of life, fatigue, cognition, and cardiopulmonary function, while calling for larger, standardized RCTs.8 Zamora and colleagues (2025) ran a PROSPERO-registered review focused on cognitive outcomes and reached a similar verdict.9 The most comprehensive analysis, Zoccali and colleagues (2026) in Diseases, identified 21 studies (including 10 RCTs) and was the first review to fold in the negative trials, concluding that HBOT appears safe and beneficial for several long COVID domains but that dose and protocol standardization remain unresolved.14 A mechanistic review by Katz and colleagues (2024), authored by clinicians at a commercial hyperbaric practice, mapped long COVID pathology to HBOT mechanisms; its industry authorship is worth noting when weighing its conclusions.7
Is there cardiac and biomarker evidence?
Yes, and it is among the more interesting findings, though each strand rests on a single study or small series. A sub-analysis of the Tel Aviv trial found HBOT reversed subclinical heart dysfunction, and biomarker studies report reductions in inflammatory and oxidative markers that align with long COVID biology.
Leitman and colleagues (2023) examined 60 patients from the original RCT with echocardiography and found 48.3% had reduced global longitudinal strain at baseline, meaning subclinical cardiac dysfunction that normal ejection-fraction testing would miss.3 In the HBOT group, GLS improved from -17.8 to -20.2 (p=0.0001, where -20 or better is normal), with a significant group-by-time interaction (p=0.041); the sham group did not change. On the biomarker side, Mrakic-Sposta and colleagues (2023) reported reduced oxidative stress and inflammatory markers after HBOT in long COVID patients,15 and a 2026 narrative review by Soedarsono and colleagues found a consistent pattern across studies: lower IL-6 and TNF-alpha, higher anti-inflammatory IL-10, and reduced reactive oxygen species.16 A detailed 2022 case report (Bhaiyat et al.) documented improvements in cognition, aerobic capacity, and lung function in a single patient after 60 sessions, with supporting perfusion and diffusion imaging.5 These mechanisms are biologically plausible (Thom, 2011; Gill and Bell, 2004; Hachmo, 2020), but plausibility is not proof of clinical benefit.171821
What protocol does the evidence actually support?
The only protocol with controlled positive evidence is 40 sessions at 2.0 ATA on 100% oxygen in a hard chamber. Short 10-session courses have failed in two randomized trials, and soft chambers at 1.3 ATA have no supporting evidence for long COVID at all. Pressure and session count both matter.
- Pressure: 2.0 ATA, which requires a medical-grade hard chamber (a soft chamber cannot reach it)
- Oxygen: 100% medical-grade oxygen
- Session length: 90 minutes, typically with intermittent air breaks
- Frequency: five sessions per week
- Total course: 40 sessions over roughly eight weeks
This matters because the chamber type is not interchangeable. The 2.0 ATA on oxygen that the trials used is only achievable in a hard-shell medical chamber, as detailed in our hard-shell versus soft-shell chamber comparison. Long COVID is not an FDA-cleared indication for HBOT, so any use is off-label; the FDA lists it among conditions where HBOT is not proven, and the recognized FDA-cleared indications are catalogued by the UHMS.2526 Reported side effects across these trials were mild and reversible, most commonly ear barotrauma (Heyboer, 2017; Camporesi, 2014).2324 How this compares to related conditions is covered in our long COVID versus ME/CFS piece and the broader HBOT for chronic conditions overview.
What are the limitations of the current evidence?
The limitations are significant and should temper any decision. The positive controlled evidence rests on one research group, sample sizes are small, protocols are inconsistent, long-term data is thin, and no biomarker yet predicts who will respond.
Source concentration. The landmark RCT, the cardiac sub-analysis, and the long-term follow-up all came from the Efrati group at the Sagol Center. The work is rigorous and peer-reviewed, but independent replication from other centers would strengthen it substantially. The biomarker studies from other countries offer partial, indirect confirmation.
Small samples and null trials. The largest RCT had 73 patients, and the two well-powered randomized trials that tested short courses found nothing. For a condition affecting tens of millions, multi-center trials of several hundred patients using the 40-session protocol are needed before firm conclusions are possible.
Protocol and prediction gaps. Studies varied in pressure (2.0 to 2.5 ATA), session count (10 to 60), and duration. The registry shows a meaningful minority worsen, yet no clinical or imaging marker reliably predicts response, which leaves patients weighing a costly, weeks-long commitment without a way to gauge their odds in advance.
Trials can be searched at ClinicalTrials.gov under “hyperbaric oxygen long COVID.” For the wider research landscape, see our HBOT research hub and, for how oxygen protocols apply to brain and nerve symptoms, our hyperbaric chamber for neurological conditions guide. Fatigue specifically is addressed in HBOT for long COVID fatigue.
Frequently asked questions
Does hyperbaric oxygen therapy work for long COVID?
The evidence is mixed. One sham-controlled RCT of 73 patients found moderate improvements in cognition, fatigue, mood, and pain after 40 sessions at 2.0 ATA (Zilberman-Itskovich, 2022), and a 232-patient registry saw 65% improve (van Berkel, 2025). But two 2025 randomized trials using 10-session courses found no benefit, and 15% of registry patients worsened. HBOT shows promise at the full 40-session dose but is not proven, and long COVID is not an FDA-cleared indication.
How many HBOT sessions does long COVID require?
The only controlled positive results used 40 sessions at 2.0 ATA over about eight weeks (Zilberman-Itskovich, 2022). Both randomized trials that tested 10-session courses failed to beat placebo (Kjellberg, 2025; D’hoore, 2025). The comprehensive 2026 review identified session count as the key variable separating positive from negative trials (Zoccali, 2026). Short courses currently have no supporting evidence for long COVID.
Can a soft-shell home chamber help with long COVID?
There is no evidence for it. Every positive study used a hard-shell medical chamber at 2.0 ATA on 100% oxygen, a pressure a soft chamber capped at 1.3 ATA cannot reach. No trial has shown a soft chamber producing the outcomes reported for clinical HBOT in long COVID. The chamber difference is explained in our hard-shell versus soft-shell comparison.
Is HBOT for long COVID safe?
In the published trials, side effects were mild and reversible, most often ear barotrauma that resolved on its own (Heyboer, 2017; Camporesi, 2014). The HOT-LoCO interim safety report confirmed the protocol was well tolerated (Kjellberg, 2023). The larger caution is not acute harm but the 15% of registry patients who reported worsening quality of life, which is why monitoring and realistic expectations matter (van Berkel, 2025).
Sources
- Zilberman-Itskovich S, Catalogna M, Sasson E, et al. “Hyperbaric oxygen therapy improves neurocognitive functions and symptoms of post-COVID condition: randomized controlled trial.” Scientific Reports. 2022;12:11252. PMID: 35821512. DOI: 10.1038/s41598-022-15565-0
- Catalogna M, Sasson E, Hadanny A, et al. “Effects of hyperbaric oxygen therapy on functional and structural connectivity in post-COVID-19 condition patients: A randomized, sham-controlled trial.” NeuroImage: Clinical. 2022;36:103218. PMID: 36208548. Link
- Leitman M, Fuchs S, Tyomkin V, et al. “The effect of hyperbaric oxygen therapy on myocardial function in post-COVID-19 syndrome patients: a randomized controlled trial.” Scientific Reports. 2023;13. PMID: 37301934. DOI: 10.1038/s41598-023-36570-x
- Hadanny A, Zilberman-Itskovich S, Catalogna M, et al. “Long term outcomes of hyperbaric oxygen therapy in post covid condition: longitudinal follow-up of a randomized controlled trial.” Scientific Reports. 2024;14:3604. PMID: 38360929. DOI: 10.1038/s41598-024-53091-3
- Bhaiyat AM, Sasson E, Wang Z, et al. “Hyperbaric oxygen treatment for long coronavirus disease-19: a case report.” Journal of Medical Case Reports. 2022;16:80. DOI: 10.1186/s13256-022-03287-w
- Robbins T, Gonevski M, Clark C, et al. “Hyperbaric oxygen therapy for the treatment of long COVID: early evaluation of a highly promising intervention.” Clinical Medicine (London). 2021;21(6):e629-e632. PMID: 34862223. DOI: 10.7861/clinmed.2021-0462
- Katz AA, Wainwright S, Kelly MP, Albert P, Byrne R. “Hyperbaric oxygen effectively addresses the pathophysiology of long COVID: clinical review.” Frontiers in Medicine. 2024;11:1354088. DOI: 10.3389/fmed.2024.1354088
- Wu BQ, Liu DY, Shen TC, et al. “Effects of Hyperbaric Oxygen Therapy on Long COVID: A Systematic Review.” Life. 2024;14(4):438. PMID: 38672710. DOI: 10.3390/life14040438
- Zamora F, Santos AC, Zamora AV, et al. “Hyperbaric Oxygen Treatment for Long-COVID syndrome: A Systematic Review of Current Evidence on Cognitive Decline.” Undersea and Hyperbaric Medicine. 2025. PMID: 41223394. Link
- van Berkel J, Lalieu RC, Joseph D, et al. “Hyperbaric oxygen therapy for long COVID: a prospective registry.” Scientific Reports. 2025;15:28351. PMID: 40759992. DOI: 10.1038/s41598-025-11539-0
- Kjellberg A, Hassler A, Boström E, et al. “Ten sessions of hyperbaric oxygen versus sham treatment in patients with long covid (HOT-LoCO): a randomised, placebo-controlled, double-blind, phase II trial.” BMJ Open. 2025;15(4):e094386. PMID: 40228859. Link
- Kjellberg A, Abdel-Halim L, Hassler A, et al. “Hyperbaric oxygen therapy for long COVID (HOT-LoCO), an interim safety report from a randomised controlled trial.” BMC Infectious Diseases. 2023;23:33. DOI: 10.1186/s12879-023-08002-8
- D’hoore L, Germonpré P, Rinia B, et al. “Effect of normobaric and hyperbaric hyperoxia treatment on symptoms and cognitive capacities in Long COVID patients: a randomised placebo-controlled, prospective, double-blind trial.” Diving and Hyperbaric Medicine. 2025;55(2):104-113. PMID: 40544138. DOI: 10.28920/dhm55.2.104-113
- Zoccali F, Fratini C, Pennacchia F, et al. “Hyperbaric Oxygen Therapy on Long COVID Symptoms: A Breath of Fresh Air.” Diseases. 2026;14(2):60. DOI: 10.3390/diseases14020060
- Mrakic-Sposta S, Vezzoli A, Garetto G, et al. “Hyperbaric Oxygen Therapy Counters Oxidative Stress/Inflammation-Driven Symptoms in Long COVID-19 Patients: Preliminary Outcomes.” Metabolites. 2023;13(10):1032. DOI: 10.3390/metabo13101032
- Soedarsono S, Wijaya RA, Biutifasari V. “Potential Biomarkers and Inflammatory Modulation of Hyperbaric Oxygen Therapy in Long COVID: A Narrative Update.” Jurnal Respirasi. 2026;12(1):90-96. DOI: 10.20473/jr.v12-i.1.2026.90-96
- Thom SR. “Hyperbaric oxygen: its mechanisms and efficacy.” Plastic and Reconstructive Surgery. 2011;127 Suppl 1:131S-141S. PMID: 21200283. Link
- Gill AL, Bell CNA. “Hyperbaric oxygen: its uses, mechanisms of action and outcomes.” QJM. 2004;97(7):385-395. PMID: 15208426. Link
- Efrati S, Fishlev G, Bechor Y, et al. “Hyperbaric Oxygen Induces Late Neuroplasticity in Post Stroke Patients: Randomized, Prospective Trial.” PLoS One. 2013;8(1):e53716. DOI: 10.1371/journal.pone.0053716
- Boussi-Gross R, Golan H, Fishlev G, et al. “Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumatic Brain Injury: Randomized Prospective Trial.” PLoS One. 2013;8(11):e79995. PMID: 24260334. Link
- Hachmo Y, Hadanny A, Abu Hamed R, et al. “Hyperbaric oxygen therapy increases telomere length and decreases immunosenescence in isolated blood cells: a prospective trial.” Aging. 2020;12(22):22445-22456. PMID: 33206062. DOI: 10.18632/aging.202188
- Harch PG. “Systematic Review and Dosage Analysis: Hyperbaric Oxygen Therapy Efficacy in Mild Traumatic Brain Injury Persistent Postconcussion Syndrome.” Frontiers in Neurology. 2022;13:815056. PMID: 35370898. DOI: 10.3389/fneur.2022.815056
- Heyboer M, Sharma D, Santiago W, McCulloch N. “Hyperbaric Oxygen Therapy: Side Effects Defined and Quantified.” Advances in Wound Care. 2017;6(6):210-224. PMID: 28616361. DOI: 10.1089/wound.2016.0718
- Camporesi EM. “Side effects of hyperbaric oxygen therapy.” Undersea and Hyperbaric Medicine. 2014;41(3):253-257. PMID: 24984321. Link
- U.S. Food and Drug Administration. “Hyperbaric Oxygen Therapy: Get the Facts.” Consumer Update. Link
- Undersea and Hyperbaric Medical Society. “Hyperbaric Oxygen Therapy Indications” (approved indications list). 2020. Link
Medical Disclaimer
The content on BaricBoost.com is for informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Author
Seph Fontane Pennock is the founder of BaricBoost.com and Regenerated.com, a clinic directory for regenerative medicine serving 10,000+ providers across the United States. He previously built and sold PositivePsychology.com, which grew to 19 million users and became the largest evidence-based positive psychology resource on the web. Seph brings direct experience as an HBOT patient, having completed protocols at clinics across three continents while navigating mold illness, systemic inflammation, and autoimmune conditions. His treatment journey includes hyperbaric oxygen therapy, peptide protocols, NAD+ therapy, and consultations with specialists from Dubai to Cape Town to Mexico. This combination of entrepreneurial track record and lived patient experience shapes everything published on BaricBoost.com. Every article is grounded in peer-reviewed research, informed by real clinical encounters, and written for patients making high-stakes treatment decisions. Seph's focus is on bringing transparency, scientific rigor, and practical guidance to the hyperbaric oxygen therapy space.
