Despite the importance of healthy settings for health promotion, little is known about how neighborhood characteristics affect men’s health. The present study aims to explore the associations between perceptions of home and workplace neighborhoods with diverse health outcomes, and to examine mediating mechanisms. A sample of 669 men members of labor unions in Quebec, Canada, completed a questionnaire assessing social and physical aspects of their work and home neighborhoods (the Health-Promoting Neighborhood Questionnaire) as well as subjective and objective health outcomes (perceived health, positive mental health, body mass index) and potential mediators (health behaviors, self-efficacy). Structural equation modeling (path analysis) revealed that the Health-Promoting Neighborhood Questionnaire was associated with all three health outcomes, either directly or indirectly through health behaviors and self-efficacy. Both home and workplace neighborhoods were associated with men’s health, home neighborhood being more strongly associated. The findings suggest that physical and social aspects of neighborhood might contribute to men’s health. The study highlights positive environmental levers for urban planners, policy makers, and health professionals to promote men’s health.