The outbreak of coronavirus disease 2019 (COVID-19) is having a dramatic effect on the mental health of healthcare workers (HCWs). Upon the emergence of the COVID-19 pandemic, the Chinese government dispatched about 42 000 HCWs to Wuhan City and Hubei Province to fight this pandemic. This study briefly examines front-line nurses who experienced burnout, with the main objective of investigating the mediating roles of positive and negative affect in the relationship between resilience and burnout in Wuhan hospitals at the peak of the COVID-19 pandemic. A total of 180 front-line nurses voluntarily participated via a social media group. They completed the online questionnaires, including the Maslach Burnout Inventory-General Survey (MBI-GS), the Positive and Negative Affect Schedule (PANAS), the Connor-Davidson Resilience Scale (CD-RISC), demographics, and work-related characteristics. Structural equation modelling (SEM) analysis was used to examine the mediating effect of positive and negative affect on the relationship between resilience and burnout. The total prevalence of burnout was 51.7%, of which 15.0% were severe burnout. These preliminary results revealed that positive and negative affect fully mediated the effects of resilience on burnout, emotional exhaustion, depersonalization, and reduced personal accomplishment of front-line nurses. It is necessary to know the impact of resilience on HCWs with burnout through the positive and negative affect of individual backgrounds and situations, and how policymakers can deploy resilience interventions to support front-line HCWs.