Purpose: Patients with psychogenic nonepileptic seizures (PNES) rate their health-related quality of life (HRQOL) more poorly than those with epileptic seizures (ES). This has been explained in part by mood state. We sought to investigate whether HRQOL differences between diagnostic groups (PNES vs. ES) can be explained by additional, perhaps chronic, aspects of mood and personality. An understanding of these relationships may inform treatment designed to improve HRQOL in ES or PNES. Methods: One-hundred fourteen individuals (69 ES and 45 PNES) completed the quality of life in Epilepsy-89. The profile of mood states (POMS) and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) were employed to measure current and chronic mood symptoms, respectively. Multiple regression analyses determined the contribution of chronic mood symptoms to HRQOL beyond the variance accounted for by current mood state and seizure diagnosis. Results: Similar to previous reports, individuals with PNES reported poorer HRQOL than those with ES. Current mood state was strongly related to HRQOL and appeared to moderate the relationship between seizure diagnosis and HRQOL. However, when more chronic psychological symptoms, such as somatization and emotional distress, were included in a model, the moderating role of mood state was not significant. Conclusion: Analyzed independently, mood state is related to HRQOL, but when chronic indicators of psychological symptoms are included in a model mood is related to HRQOL, but, the moderating effect of mood is no longer significant. Treatments designed to improve HRQOL among individuals with intractable seizures should also address chronic psychological distress and symptoms associated with high levels of somatization. © 2007 International League Against Epilepsy.