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Purpose : This study is to identify job stress and quality of life in health managers with over two years’ experience, working in large workplaces (300+ full-time workers) since COVID-19. Methods : The data were collected from 125 health managers through an online survey from October 28 to November 3, 2021 with an IRB approval and analyzed. The statistical methods included t-test, variance analysis, Pearson correlation, and hierarchical regression. Results : Health managers experienced high job demands, low autonomy, and insecurity. Gender differences were observed in job demands and autonomy. Quality of life was lower in physical health but higher in the psychological area. Various personal and workplace characteristics influenced the differences in job stress and quality of life. Strong correlations were found between job stress and quality of life sub-areas. Conclusion : To reduce job stress and enhance health managers' quality of life in large workplaces, organizational measures, physical health programs, and differentiated approaches based on personal and workplace characteristics are recommended. Addressing key stressors such as relationship conflict, inadequate compensation, and workplace culture is crucial for improvement. These suggestions aim to create a more suitable working environment for health managers' responsibilities in health and safety.