In patients with epilepsy (PWE), relationships between depression, epilepsy characteristics, and cognitive aspects are complex. This study aimed to assess the occurrence of possible major depressive episode in PWE and to verify whether it is associated with the clinical aspects of the disease and cognition.Two hundred consecutive PWE with a mean age and standard deviation of 47.6 (±15.1) years were included in the study. We determined whether their Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) scores were associated with their clinical, cognitive, and QOLIE-31 aspects using a significance level of 5% (p15, suggestive of major depressive episode. Logistic regression showed that NDDI-E >15 was associated with seizure frequency (p=0.022) and worse performance in the category fluency test (p=0.003). An NDDI-E >15 was also correlated with lower quality of life (p<0.001).The present findings suggest that possible major depressive episode is associated not only with epilepsy characteristics but also with cognitive aspects, such as category fluency, and quality of life.