BackgroundGender differences have been reported in the severity and psychopathological features of major depressive disorders among adults but are poorly reported in adolescent samples.ObjectiveThis study aimed to examine gender differences in the psychopathology of mixed depression among adolescents.MethodsWe analyzed 341 outpatients with the current major depressive episode (MDE) retrospectively to identify patients with DSM-5 MDE with mixed features. We compared examiner-rated depressive and (hypo)manic symptoms and self- and parent-reported symptoms between sexes.ResultsWe identified 76 patients with an MDE with mixed features (67.1% females, 32.9% with bipolar disorder). Depression severity was significantly greater in femalesversusmales (CDRS-R total score 56.2vs. 48.2, p = 0.014). Depressive symptoms were significantly and independently found to be more severe among females in a logistic regression model, including excessive fatigue (OR 1.68; p = 0.025), low self-esteem (OR 1.67; p = 0.04), excessive weeping (OR 1.62; p = 0.021), and CBCL AAA index (OR 1.04; p = 0.015). None of the depressive symptoms scored greater in males. Males had higher levels of motor activity (2.12vs. 1.69; p = 0.048) and pressured speech (1.80vs. 1.24; p = 0.004). Self-rated anxiety (69.3vs.56.8, p = 0.047) and CBCL AAA index (207vs.189; p = 0.007) were higher in females.ConclusionAdolescent depression with mixed features is more severe in women, with a higher expression of core affective symptoms and excessive fatigue. While in males, slightly higher levels of psychomotor activation are reported, in females, emotional dysregulation and excessive weeping may subtend a difference in a broader spectrum of mixed features.