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Aim We explored the impact of job content and stress on anxiety, depressive symptoms and self-perceived health status among nurse practitioners ( NPs). Background Taiwan's NP roles vary between hospitals as a result of the diverse demands and complex tasks that cause job-related stress, potentially affecting the health of the NP. Methods This study utilised a cross-sectional descriptive design with 161 NPs from regional hospitals participating. Data collection involved demographics, the Taiwan Nurse Stress Checklist, the Job Content Questionnaire, the Beck Anxiety Inventory, the Beck Depression Inventory, a General Health Status Checklist and salivary cortisol tests. Results NPs reported moderate job stress, similar job control to nurses, mild anxiety and depression, and below-average self-perceived health. Being a licensed NP, personal response, competence, and incompleteness of the personal arrangements subscales of job stress, and anxiety predicted self-perceived health after adjusting for other covariates. Conclusions Job stress and anxiety affect NP health. Implications for Nursing Management NPs are a valuable resource, and the healthcare system demand is growing. Reasonable NP staffing, working hours, proper promotion systems, the causes of job stress, job content clarification and practical work shift scheduling need to be considered. The occupational safety and physical and psychological health of NPs are strongly associated with the quality of patient care. [ABSTRACT FROM AUTHOR]