Given the lack of active nurses in industrialized countries throughout the world, in combination with demographic changes, it is of utmost importance to protect nurses’ well-being and to prevent psychological distress, because of their strong association with premature occupational leave. The aim of this study was to investigate the effects of quality of leadership and social support at work on well-being and psychological distress of nurses and to determine whether nurses’ overcommitment mediates the relationship between the abovementioned determinants and the outcomes. A cross-sectional survey design was used to gather our data. This study utilized part of the database of the Nurses’ Early Exit Study. A total of 34,771 nurses (covering all nurse qualifications) working in hospitals, nursing homes, and home-care institutions in 8 European countries filled out a questionnaire (response rate = 51.4%). For all model variables (job satisfaction, satisfaction with salary, positive affectivity, personal burnout, negative affectivity, quality of leadership, social support from immediate supervisor, social support from near colleagues, and overcommitment), psychometrically sound, that is, valid and reliable measures were used. Outcomes from testing a structural equation mediation model indicated that, respectively, positive and negative influences of leadership quality and social support from supervisor and colleagues on nurses’ well-being and psychological distress are partially mediated, that is, reduced, by nurses’ overcommitment. Social work environment is highly important in relation to nurses’ well-being and psychological distress.