Fibromyalgia syndrome (FMS) is characterized by longstanding multifocal pain with generalized allodynia/hyperalgesia. There are several treatment methods but none has been specifically approved for this application. We conducted a randomized controlled study to evaluate the effect of hyperbaric oxygen (HBO) therapy in FMS (HBO group: n = 26; control group: n = 24). Tender points and pain threshold were assessed before, and after the first and fifteenth sessions oftherapy. Pain was also scored on a visual analogue scale (VAS). There was a significant reduction in tender points and VAS scores and a significant increase in pain threshold of the HBO group after the first and fifteenth therapy sessions. There was also a significant difference between the HBO and control groups for all parameters except the VAS scores after the first session. We conclude that HBO therapy has an important role in managing FMS.