Purpose: This study aimed to confirm the mediating effect of social responsibility on the relationship between nurses' stress and burnout from coronavirus disease (COVID-19) in tertiary general hospitals. Methods: For this descriptive cross-sectional study, online survey data from 193 nurses in three tertiary general hospitals were analyzed. Data were collected from March 30 to April 4, 2021. The following statistical analysis were conducted: t-test, ANOVA, Scheffé test, Pearson's correlation coefficient analysis, and Hayes Process Macro Model 4 (to test the mediating effect). Results: COVID-19 stress was positively associated with burnout (r=.28, p<.001) and social responsibility (r=.22, p=.002). Social responsibility was negatively associated with burnout (r=-.31, p<.001). Furthermore, the mediation analysis indicated that social responsibility mediated the relationship between COVID-19 stress and burnout. Conclusion According to the results, the impact of COVID-19 stress on the burnout was mediated by social responsibility. Therefore, to prevent the burnout from COVID-19 of nurses, developing educational programs to enhance social responsibility are recommended.