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Objective: This study aimed to investigate the prevalence of depression and anxiety, examine how different shift work schedules (day, evening, night, and rotation) relate to mood and anxiety disorders in female nurses in Saudi Arabia, and identify the least impactful shift in mental health.

Methods: This was a cross-sectional, community-based study that used validated questionnaires to assess depression Patient Health Questionnaire (PHQ-9) and anxiety Generalized Anxiety Disorder (GAD-7) in female nurses in Saudi Arabia.

Results: The study included 418 female nurses in Jeddah, Saudi Arabia. The majority of them were aged 25-34 years and had Indian nationality. Most nurses were married, held a diploma degree, and had 10-20 years of experience. Around 33% experienced minimal or no depression, and 49.3% had minimal or no anxiety, while the rest experienced mood disorders during their working shifts. Day shifts were the least associated with depression and anxiety. While rotating shifts were significantly associated with no depression. Previous mental disorders (OR= 2.6) and the working department (Pediatric Ward)(OR= 0.12) were two significantly associated factors with poor quality of life in nurses.

Conclusion: Depression and anxiety were common during work shifts. Daytime shifts had lower levels of mood disorders, and rotating shifts showed no significant depression. Tailored interventions are crucial for fostering resilience and enhancing patient care.