Determine changes in cognition and post-traumatic stress disorder (PTSD) symptoms in subjects with traumatic brain injury (TBI) exposed to 2.4 atmospheres absolute (atm abs) breathing 100% oxygen vs. sham (1.3 atm-abs air).Fifty randomized subjects completed a total of 30 exposures. A concussion history was taken, then baseline, post-series, and six-week follow-up immediate post-concussion assessment and cognitive testing, Brain-checkers and PTSD Checklist for Military (PCL-M) tests were administered.No statistically significant differences between groups were noted, but both groups improved. Subgroups analyses, based on concussion history and individual test components, showed improvement in the treatment group vs. the sham. These subgroups included the number of concussive events, time from event to consent, loss of consciousness, visual memory, processing, go--no go, and simple reaction time.There was no statistically significant difference between a sham and 2.4 atm abs hyperbaric oxygen (HBO2) in cognitive scores from ImPACT and Brain-checkers or composite scores in the PCL-M; however both groups showed improvement. Subgroups with favorable response to treatment are identified. Future studies evaluating HBO2 should consider concussion histories or focus on validating subgroup response to determine HBO2 as a potential adjunctive treatment for persistent symptoms following TBI.