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Purpose: The purpose of the study was to investigate the mediating effects of psychosocial well-being on the relationship between self-leadership and learning flow in nursing students. Methods: A total of 148 nursing students with online class experience participated in the study. The data were analyzed using the independent t-test, Pearson’s correlation coefficient, PROCESS macro, and bootstrapping methods with SPSS Statistics 26.0. Results: The results showed that self-leadership, learning flow, and psychosocial well-being were significantly correlated, and self-leadership had a direct effect on learning flow. In other words, the higher the level of self-leadership, the higher the learning flow of nursing students. Psychosocial well-being was partially mediated by self-leadership and learning flow. Conclusion: It is necessary to develop and implement programs for self-leadership and psychosocial well-being enhancement as a strategy to enhance nursing students’ learning flow.