The present review evaluated the effect of hyperbaric oxygenation (HBO) therapy on post-concussion syndrome (PCS). Searches for publications from the earliest date possible up until the first week of 2016 were conducted using the electronic databases Cochrane, EBSCOhost, Embase, Ovid MEDLINE, PubMed and Web of Science. Additional trials were identified through reference list scanning. Randomized controlled trials assessing the effectiveness of HBO therapy in PCS were selected and tested for eligibility for inclusion in the present review. Two independent reviewers conducted data extraction and the Cochrane Collaboration's recommended method was used to assess the risk of bias in each study included. Review Manager 5.3 software was used for data synthesis and analysis and the standardized mean difference (SMD) or mean difference (MD) was estimated with a fixed or random effects model using a 95% confidence interval (CI). A total of 127 articles were identified, 4 of which were eligible for final analysis. The meta-analysis identified no difference in the Rivermead Post-Concussion Symptoms Questionnaire (MD=1.23; 95% CI, −3.47-5.94; P>0.05; I2=35%) or Post-Traumatic Stress Disorder Checklist (PCL) scores (SMD=0.12; 95% CI, −0.31-0.54; P>0.05; I2=0%) scores between groups receiving different oxygen doses. The differences in PCL scores (SMD=−0.13, 95% CI, −0.80-0.53; P>0.05; I2=63%) and neurobehavioral symptoms (SMD=−1.00, 95% CI, −2.58-0.58; P>0.05; I2=92%) between the HBO and sham groups were not significant. The current study demonstrated that HBO therapy has no significant effect on PCS compared with the sham group. Therefore, it was determined that effective design and execution of a large clinical trial, which includes treatment, control and sham groups is required in the future.