Background: Gender differences have been reported in the severity and psychopathological features of major depressive disorders among adults but are poorly reported in adolescent samples. Objective: This study aimed to examine gender differences in the psychopathology of mixed depression among adolescents. Methods: We 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. Results: We identified 76 patients with an MDE with mixed features (67.1% females, 32.9% with bipolar disorder). Depression severity was significantly greater in females versus males (CDRS-R total score 56.2 vs. 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 (2.12 vs. 1.69; p=0.048) and pressured speech (1.80 vs. 1.24; p=0.004). Self-rated anxiety (69.3 vs 56.8, p=0.047) and CBCL AAA index (207 vs 189; p=0.007) were higher in females. Conclusion: Adolescent 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.