Depression is associated with profound impairments in social and interpersonal functioning. However, little research has addressed deficits in mentalizing capacity that may underlie these impairments. The aim of this study was, therefore, to investigate the capacity for mentalization in female inpatients with depression in comparison with healthy controls. We assessed 46 inpatients with major depressive disorder with regard to psychiatric diagnoses, severity of depression, cognitive impairment, and verbal intelligence. In addition, 20 healthy controls matched for sex, age, and education were included. Mentalization was scored on the Adult Attachment Interview using the Reflective Functioning Scale. The female inpatients with depression showed a significantly lower capacity for mentalization compared with the healthy controls. Mentalization deficits were not restricted to depression-specific topics. Moreover, deficits in mentalizing capacity were related to illness duration, number of admissions, and cognitive impairment. The results indicate severe impairment in the ability of the female inpatients with depression to identify and interpret mental states of the self and others. Correlations with illness duration and number of admissions suggest that a chronic course of depression results in further mentalizing impairments. The investigation of mentalization may be of particular importance for the development of targeted psychotherapeutic interventions for depression.