There is a lack of comparable health-related quality of life (HRQoL) and utility data across all mental disorders and all inpatient and outpatient settings. Our objective was to investigate the HRQoL and utility scores of people with mental disorders in France, treated in outpatient and inpatient settings, and to identify the HRQoL and utility score losses attributable to mental disorders compared to the non-mentally ill general population. A cross-sectional survey was conducted to assess HRQoL (SF-12) and utility scores of patients with mental disorders and followed in four psychiatric sectors in France. Scores were described by demographic and clinical characteristics and were then adjusted on age and gender and compared with those of the non-mentally ill general population. Median HRQoL and utility scores were significantly lower in patients with mental disorders than in the non-mentally ill general population; median differences amounted to 5.4 for the HRQoL physical score, to 11.8 for the HRQoL mental score and to 0.125 for the utility score. Our findings underscore the negative impact of mental disorders on HRQoL in France and provide a baseline to assess the global impact of current and future organizational changes in the mental health care system.