A cross-sectional survey was conducted, with the aim to examine what stressors in the workplace and demographic factors were associated with signs and symptoms of poor well-being among psychiatric nurses. A structured questionnaire was distributed to nurses within six psychiatric hospitals in Japan. Information was collected on demographic information, work characteristics and two dimensions of well-being: feeling uptight and emotional exhaustion. Three hundred and sixty-one questionnaires were completed by participants. High rates of emotional exhaustion in psychiatric nurses were found to be predicted by young age, high psychological demands paired with low social support in the workplace, job strain (a proxy to occupational stress) and job strain paired with low social support. In addition, high rates of being tense/uptight were associated with high psychological job demand, low psychological job control, low social support in the workplace, high job strain and high job strain paired with low social support. The current study has found evidence of significant relationships between demographic factors and several work and organizational stressors and poor mental health among Japanese psychiatric nurses.