Depression in children and adolescents with epilepsy is common. Depression worsen quality of life in epilepsy patients. Neurobiological, social, and iatrogenic factors may play a role in depressive disorder development. We report a patient with partial epilepsy secondary to neonatal stroke, who developed depressive disorder as a result of levetiracetam (LEV) treatment. Our report illustrates the possible implication of iatrogenic factors in depression among epilepsy patients. However, recent data suggest that LEV may be effective in case of affective disorders. We discuss the factors linking epilepsy with depression. Because of its high incidence and its multiple physiopathologic factors, psychiatric comorbidity should be always assessed in pediatric epileptic patients.