Background: Impaired Quality of life (QoL) in schizophrenia has been mostly associated with psychotic and mood symptomatology, insight and functioning so far. Aims: QoL levels remain unsatisfactory due to other factors we aim to explore. Method: We have explored sleep quality with the Pittsburgh Sleep Quality Index, hostility with the Buss&Perry questionnaire, major depression with the Positive and Negative Syndrome Scale depressive factor, functioning with the Global Assessment of Functioning scale and weight gain with body mass index in addition to other classical QoL-associated factors. Results: 559 patients (mean age=31 (SD 9) years, 74% male sex) were included in the national FACE-SZ cohort. Impaired QoL has been significantly associated with respectively major depression, impaired sleep quality, increased hostility, impaired functioning and impaired insight independently of age, sex, treatments, tobacco smoking and body mass index. Major depression was associated with impaired psychological and physical well-being, and impaired self-esteem. Impaired sleep quality has been associated with impaired psychological and physical well-being and sentimental life. Hostility has been associated with impaired psychological well-being and self-esteem, impaired friends’ relationships and impaired autonomy. Weight was associated with impaired physical well-being. Tobacco smoking was associated with higher level of friends’ relationships. Conclusions: Major depression, sleep, hostility, and weight gain have been identified as potential targets to improve QoL in schizophrenia and should be implemented in the recommendations for good practice to optimize schizophrenia care.< Réduire