Macro-level economic decline is usually assumed to affect the mental health of individuals but the process by which this occurs and factors that moderate are still not well understood. This study builds from three bodies of literature to address how economic hardship, religion and psychosocial variables affect mental health outcomes in the context of widespread economic crisis in the farm sector. (Parallels exist with other sectors where plant closings, job loss and unemployment occur.) Differential effects of economic hardship and religion were examined using a sample of 800 Ohio farm men and women who experienced the 1980s Midwestern farm crisis. Findings demonstrated that economic hardship was a consistent predictor of stress and depression for both genders. Membership in Fundamentalist denominations increased men's well-being. Affiliation with any religious group enhanced women's mental health. Physical health and social support were associated with lower stress and depression. Coping techniques had mixed effects on stress and depression with both avoidance/denial and support seeking associated with more adverse mental health outcomes. This study shows that macro-level structural changes can result in a context of economic hardship where factors assumed to buffer adverse mental health outcomes fail to do so and where previously neglected factors, such as religion, become important mediators of hardship.