Hyperbaric oxygen therapy (HBOT) was conducted on two male patients with chronic prostatitis/chronic pelvic pain syndrome who were resistant to conventional medical therapies. Both patients underwent 20 sessions of 100% oxygen inhalation (2.0 atmosphere absolute for 90 min/day, five days/week for four weeks) in a hyperbaric chamber. The follow-up period was three months. Although the patients reported a slight improvement in the pain domain of the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) after HBOT, no changes were noted in the other domains of NIH-CPSI and International Prostate Symptom Score. No adverse events were encountered during or after HBOT.