Combat veterans often return from deployment having experienced a wide range of exposures, symptoms, and medical conditions. The Department of Veterans Affairs established war-related illness and injury study centers to serve combat veterans with unexplained illnesses. We report the exposures, clinical status, and utilization of 53 combat veterans who participated in the National Referral Program (NRP) from January 2002 until March 2004. Participants were primarily male (81%) and served in the Persian Gulf War (79%). Common diagnoses were chronic fatigue syndrome (n = 23, 43%), neurotic depression (n = 21, 40%), and post-traumatic stress disorder (n = 20, 38%). Self-reported exposures related to weaponry, disease prophylaxis, environmental hazards, stress, and poor hygiene. A small increase in mean SF-36V mental component scores (2.8 points, p = 0.009) and use of rehabilitation therapies (1.6 additional visits, p = 0.018) followed the NRP referral. The small gain in mental function suggests that the NRP may benefit combat veterans with long and complex medical histories.