Comorbid psychiatric conditions are highly prevalent in patients with epilepsy, yet the long-term implications across multiple mental health conditions are poorly understood. We examined the association between psychiatric diagnoses and self-reported health status in veterans with epilepsy. ANCOVA models were used to derive adjusted SF-36V scores for individuals with epilepsy alone (N=7379) or with additional psychiatric conditions (N=6320): depression, schizophrenia, bipolar disorder, anxiety disorder, substance abuse, and posttraumatic stress disorder (PTSD). Compared with patients with epilepsy alone, scores of veterans with comorbid psychiatric diagnoses averaged 21% lower across all domains. Role Limitation scales exhibited the greatest decrement across domains. A PTSD diagnosis consistently corresponded to lower scores, followed by depression. Schizophrenia contributed the least detriment to perceived health status. Comorbid psychiatric conditions impart significant emotional and physical burdens, requiring timely recognition and treatment of these disorders. Patients with epilepsy are uniquely at risk for high physical-psychiatric comorbidity profiles, with concomitant losses in perceived health status.