Depression is common among patients with epilepsy. The aim of our study was twofold: to estimate the prevalence of a major depressive episode and to identify its determinants among patients with epilepsy treated in the largest Greek hospital in Athens.All consecutive patients with epilepsy that visited the epilepsy outpatient clinic of Evangelismos General Hospital were invited to participate in the study. Ninety-four patients met our inclusion criteria.A diagnosis of a current major depressive episode was established in 21 out of 94 eligible to participate (22.3%) patients. Being a female was associated with a 19.68-fold increase in the odds of having a major depressive episode (95% CI 3.39–114.14, p=0.001); being unemployed was associated with a 6.46-fold increase in the odds of having a major depressive episode (95% CI 1.23–34.07, p=0.028), and each extra seizure experienced per month was associated with a 1.38-fold increase in the odds of having a major depressive episode (95% CI 1.03–1.85, p=0.031).Unemployment, female gender, and seizure control are important determinants of a major depression episode among patients with epilepsy.