Objective: To explore the factors that lead to occupational burnout among nurses in pediatric infectious disease wards after two consecutive years of frontline anti-epidemic work since the admission of COVID-19 patients in January 2020, in order to lay a scientific basis for reducing nurse occupational burnout. Methods: A total of 12 nurses who working in pediatric infection units were included in the study. Utilizing qualitative research methodologies, we used semi-structured interviews as the primary data collection method. The interview data underwent meticulous organization and were subjected to descriptive analysis. Results: 12 nurses assigned to pediatric infection wards frequently encounter occupational burnout, primarily attributed to increased work intensity, nurse-patient relationships, occupational frustration, psychological pressure, hospital infections, and various other contributing factors. Conclusion: We found that the severity of occupational burnout among nurses specializing in pediatric infectious diseases is noteworthy. Our recommendations include heightened consideration of this issue by government authorities and hospital administrators.