Depressive symptoms, in addition to positive and negative symptoms, are commonly observed in the course of schizophrenia. These symptoms may cause disability and reduced self-esteem. Disability and lower self-esteem may disrupt the quality of life and lead to social isolation. Demonstrating the relationships among these concepts and correcting possible disturbances may help to augment treatment compliance and improve the prognosis. In this study, the Calgary Depression Scale for Schizophrenia (CDSS), the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the World Health Organization Disability Assessment Schedule 2.0 (WHODAS), and the Rosenberg Self Esteem Scale (RSES) were applied along with a sociodemographic data form to 146 patients with schizophrenia. Path analyses were used to demonstrate the direct effect of schizophrenia severity on self-esteem and its indirect effect through disability and depression, the mediating effect of depression in the relationship between schizophrenia severity and disability, and the mediator effect of disability in the bidirectional relationship between self-esteem and depression. Statistically significant results were obtained. In multivariate regression analysis, significant effects on disability were demonstrated for PANSS General Psychopathology subscale, CDSS, and RSES. These data suggest that attention should be focused on concepts such as depression, disability, and self-esteem in schizophrenia patients.