Evidence on the relationship between burnout and post-traumatic stress disorder (PTSD) is limited. We aimed to evaluate the association between burnout and PTSD symptoms among medical staff two years after the coronavirus disease 2019 (COVID-19) pandemic in Wuhan, China, and explore the mediating roles of social support and psychological resilience.A multicenter survey was conducted online from January to March 2022 among healthcare professionals from six general hospitals. Hierarchical linear regression was used to detect the predictors of PTSD symptoms. Structural equation modeling (SEM) was used to analyze the pathways from burnout to PTSD symptoms.Hierarchical linear regression showed that burnout, social support, and psychological resilience were significant predictors of PTSD symptoms among medical staff. In the SEM, the standardized total effect of burnout on PTSD symptoms was 0.336(bias-corrected 95 % confidence interval [0.303, 0.367], P < 0.001). Social support and psychological resilience partially mediated the relationship between burnout and PTSD symptoms (indirect effects accounted for 22.3 % of the total effect).Owing to the cross-sectional design, only clues to causal explanations can be provided.Burnout has significant direct and indirect effects on PTSD symptoms. Furthermore, social support and psychological resilience might be effective ways to reduce the impact of burnout on PTSD symptoms in medical staff after a major public health outbreak.Copyright © 2022. Published by Elsevier B.V.