Purpose: This study was undertaken to confirm the mediating effect of ego-resilience between COVID-19 pendemic stress and depression in nursing students. Methods: This was a cross-sectional survey enrolling 125 nursing students who voluntarily participated in the study and had experienced the COVID-19 pandemic. Data were collected from May 1 to 22, 2022 through an online questionnaire comprising 74 questions. Data analysis was achieved using SPSS/Win 25.0 program by frequency and percentage, mean and standard deviation, independent t-test, one-way ANOVA, and pearson’s correlation. Mediation analysis was also conducted using Hayes’ PROCESS macro (Model 4). Result: The mean scores for depression was 2.87. The mediation effects in step 1 indicated that COVID-19 pandemic stress had a statistically significant negative effect on ego-resilience and a significant positive effect on depression. In step 2, ego-resilience imparted a statistically significant negative effect on depression. In step 3, complete mediating effects of ego-resilience were determined on the relationship between COVID-19 pandemic stress and depression. Conclusion: In order to improve the ego-resilience of nursing students, it is necessary to develop and apply an ego-resilience improvement program as a curriculum or extracurricular program in nursing colleges. Such endeavors will strategize in reducing depression among nursing students.