Objective We aimed to investigate the effect of nursing professionals’ resilience on their mental health, work-related stress, and anxiety in response to the COVID-19 pandemic. Methods We conducted an online survey in the Asan Medical Center and Ulsan University Hospital, South Korea. We extracted data of 824 nursing professionals who consented to participate, including demographic variables and the Stress and Anxiety to Viral Epidem-ics-9 (SAVE-9), PHQ-9, GAD-7, and Brief Resilience Scale scores. Results Resilience was negatively correlated with Patient Health Questionnaire-9 (PHQ-9) (rho=-0.23), Generalized Anxiety Scale-7 items (GAD-7) (rho=-0.25), Stress and Anxiety to Viral Epidem-ics-6 items (SAVE-6) (rho=-0.15), and Stress And anxiety to Viral Epidem-ics-3 items (SAVE-3) (rho=-0.13, all, p<0.001). Logistic regression analysis adjusting age, marital status, and years of employment revealed that high level of general anxiety [adjusted odds ratio (aOR)=1.40, 95% confidence interval (CI)=1.31–1.50], work-related stress during viral epidemics (aOR=1.16, 95% CI=1.03–1.29), and a low level of resilience (aOR=0.91, 95% CI=0.85–0.97) were expecting variables for the depression of healthcare workers. Conclusion Nursing professionals’ level of resilience may be associated with low level of work-related stress and anxiety induced by a viral epidemic. We need to explore further the possibility of resilience as coping strategy of healthcare workers in this pandemic era. Psychiatry Investig 2021;18(4):357-363