Purpose: This study investigated mediating effects of flexibility in the relationship between job stress, sleep quality, and mental well-being of psychiatric hospital workers.Methods: Data were collected from 210 subjects recruited online February 25-March 24, 2022, and hierarchical regression analysis was conducted using the SPSS program 25.0 version.Results: Regarding mental well-being of psychiatric hospital workers, findings showed statistically significant positive correlations with flexibility (r=.62, <i>p</i><.001) and sleep quality (r=.34, <i>p</i><.001), and significant negative correlation with job stress (r=-.40, <i>p</i><.001). Also, flexibility of psychiatric hospital workers showed partial mediating effect (Boot LLCI=-.64, Boot ULCI=-.13) on the relationship between job stress and mental well-being, and the complete mediating effect (Boot LLCI=-.11, Boot ULCI=.20) on the relationship between sleep quality and mental well-being.Conclusion: Since flexibility is a key factor in improving the mental well-being of psychiatric hospital workers, programs to promote flexibility are strongly recommended.