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Purpose: This study aimed to investigate the degree of role conflict and its ambiguity, and fatigue in clinical nurses and to analyze the effect of these on their self-resilience in order to provide fundamental data for improving their working environment after the Middle East Respiratory Syndrome outbreak. Methods: After the collection of data from 258 clinical nurses in five general hospitals, t-test, ANOVA, Pearson's correlation coefficient, and multiple regression were performed using IBM SPSS Statistics 20.0. Results: A significant positive correlation was found between nurses’ role conflict and ambiguity and fatigue; while a negative correlation was found between nurses’ role conflict and ambiguity and self-resilience. A significant negative correlation was found between fatigue and self-resilience. According to the study results, the factor that affected clinical nurses’ self-resilience the most was role conflict and its ambiguity, followed by marital status, fatigue, educational level, religion, and related tasks, which together accounted for 38% of self-resilience in clinical nurses. Conclusion: To improve weaknesses in nursing care after the Middle East Respiratory Syndrome outbreak, the scope of nursing care was changed upon the expansion of integrated nursing and care-giving services. Therefore, in the rapidly changing environment of nursing, policies to improve nursing performance, as well as successful reaction capability, are suggested.