Purpose: The purpose of this study was to investigate the mediating effect of self-leadership on the relationship between media literacy and learning agility in nursing students based on their experiences in online classes during the Coronavirus Disease-19 pandemic.Methods: A descriptive survey was conducted among 165 nursing students from four universities in Busan. Data were collected from June 2 to 13, 2021, and was analyzed using a t-test, one-way ANOVA, Pearson’s correlation coefficients, and stepwise multiple regression with SPSS/WIN 26.0.Results: Significant relationships were found between learning agility and media literacy (r=.62,p<.001), between learning agility and self-leadership (r=.58, p<.001), and between media literacy and self-leadership (r=.53, p<.001). Additionally, self-leadership had a partial mediating effect on the relationship between media literacy and learning agility (Z=4.30, p<.001); its explanatory power was 46.0%.Conclusion: These results indicate that interventions to increase the level of media literacy, along with self-leadership, are necessary to improve the level of learning agility of nursing students who will be essential human resources in a rapidly changing healthcare field.