Background: HRQOL is lower in patients with psychogenic non-epileptic seizures (PNES) than in epilepsy patients. Although psychopathology may reduce HRQOL, it is not known whether patients with PNES and epilepsy are similarly affected. We aimed to compare the relationship between psychopathology and HRQOL in PNES and treatment resistant epilepsy. Material/Methods: 106 patients with definite diagnosis of PNES or epilepsy were recruited from Epilepsy Monitoring Unit. Patients completed QOLIE-89, Profile of Mood States (POMS), and Adverse Events Profile (AEP). Total Mood Disturbance (TMD) was derived from POMS. We used chisquare and t tests and hierarchical multiple regression to compare HRQOL and its mental status correlates in patients with PNES and epilepsy. Results: Psychiatric history was more prevalent and depression/dejection and TMD were higher in PNES than epilepsy (P≤0.003). PNES patients had a lower adjusted mean HRQOL than epilepsy patients (P<0.01). Mood problems and AEP were strong predictors of HRQOL (P<0.001) and explained the lower HRQOL in PNES vis-à-vis epilepsy. Decreases in HRQOL due to mood problems were similar in both groups. The model explained 62% of the variation in HRQOL. Conclusions: Although more severe psychopathology in PNES explains the lower HRQOL in PNES relative to epilepsy, the negative association between psychopathology and HRQOL remains stable across the groups. PNES patients with severe mood problems show similar, low levels of HRQOL as patients with severe mood problems who have epilepsy. Future studies should examine causal linkages between psychopathology and PNES and other explanations in seizure-related QOL.