The most interesting questions in hyperbaric medicine right now are also the hardest: can pressurized oxygen help a brain injured by trauma, or one still foggy months after a COVID-19 infection? These are exactly the conditions where hope outruns proof — which makes the distinction between what has been peer-reviewed and what is merely promoted especially important.
A sham-controlled trial in long COVID
The strongest published signal comes from a randomized, double-blind, sham-controlled trial out of Israel, reported in Scientific Reports in 2022. Researchers enrolled 73 patients who had remained symptomatic for at least three months after COVID-19 and randomized them to 40 daily sessions of either hyperbaric oxygen or a sham protocol.
The HBOT group showed statistically significant improvement over sham across several cognitive domains, including global cognitive function, attention, and executive function. The trial also reported gains in energy and fatigue, sleep, psychiatric symptoms, and pain. Because the study was double-blind and sham-controlled — the design feature missing from much HBOT research — its results carry more weight than the typical uncontrolled case series.
A companion neuroimaging analysis, published in NeuroImage: Clinical the same year, reported that HBOT was associated with measurable changes in the brain’s functional and structural connectivity, offering a plausible biological correlate for the cognitive findings rather than symptom scores alone.
What’s registered and still enrolling
That long-COVID work is registered on ClinicalTrials.gov as NCT04647656, sponsored by Shamir Medical Center in Israel. It is part of a broader pipeline. For brain injury, a Phase 3 study at LSU Health Sciences Center has examined HBOT at 1.5 atmospheres for chronic mild TBI and persistent post-concussion syndrome. More recently, the University of South Florida began recruiting in 2024 for NCT06581003, a Phase 3 randomized, sham-controlled study of HBOT for veterans with traumatic brain injury, with a planned enrollment of roughly 420 participants.
The scale and rigor of these newer trials matter. Small, unblinded studies have fueled HBOT enthusiasm for years; adequately powered, sham-controlled trials are what will actually settle whether the early signals hold.
Reading the evidence honestly
A single positive trial, however well-designed, is a starting point, not a verdict. The long-COVID study was modest in size, and the brain-injury trials are still in progress. None of this has changed the regulatory status of these uses.
The FDA has cleared hyperbaric oxygen only for a specific, defined list of conditions — among them decompression sickness, carbon monoxide poisoning, certain non-healing and diabetic wounds, gas gangrene, and radiation injury. It has not cleared or approved HBOT for COVID-19, long COVID, or traumatic brain injury, all of which remain investigational. The agency has warned that treating an unproven use as established can delay effective care and cause harm.
The frontier is genuinely active, and some of the early data are encouraging. But “promising and under study” is not the same as “proven,” and patients are best served when those two ideas are kept apart.
Sources
- Scientific Reports (2022) — HBOT improves neurocognitive function in post-COVID condition (RCT)
- NeuroImage: Clinical (2022) — HBOT effects on brain connectivity in post-COVID patients
- ClinicalTrials.gov — HBOT for Post-COVID-19 Syndrome (NCT04647656)
- ClinicalTrials.gov — HBOT for Veterans With Traumatic Brain Injury (NCT06581003)
- FDA — Hyperbaric Oxygen Therapy: Get the Facts