This study explored the association between the two job-stress models, job-strain and effort-reward imbalance, and mental health outcomes in a working population exposed to major organizational changes. The cross-sectional study was based on 680 subjects, 504 men and 176 women. Psychosocial factors at work included: psychological demands, decision latitude, social support, effort, reward, and overcommitment. Mental health outcomes were depressive symptoms (CES-D) and psychiatric disorders (GHQ-12). Job strain, low decision latitude, effort-reward imbalance, and low reward (especially job instability) were found to be associated with depressive symptoms and/or psychiatric disorders among men. Overcommitment at work was a risk factor for both men and women. Social support at work played a role to reduce depressive symptoms for women. These findings emphasize the deleterious effects of psychosocial work environment on mental health during major organizational changes.