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The current cross-sectional study aimed to explore the relationship between work stressors and mental health in frontline nurses exposed to COVID-19. Participants were recruited from 16 general hospitals in Anhui province from February 2020 to March 2020. The general sociodemographic questionnaire, Nurse Job Stressors Scale, Simplified Coping Style Questionnaire, NEO Five-Factor Inventory, Perceived Social Support Scale, and Kessler Psychological Distress Scale were used in this study. Based on 723 valid questionnaires retrieved (100%),