ObjectiveTo explore the current status and interaction of perceived stress, job burnout and mental health among healthcare workers after the opening of COVID-19 which occurred in December 2022.MethodsA cross-sectional study of 792 healthcare workers from three tertiary hospitals in Wuxi was conducted from January 2023 to February 2023. Sociodemographic questionnaire, Perceived Stress Scale, Burnout Scale and Mental Health Self-Assessment Questionnaire were used for investigation. SPSS 26.0 was used to conduct data analysis. The significance of mediation was determined by the PROCESS macro using a bootstrap method.ResultsThe results showed that (1) The average scores of the participants for perceived stress, mental health and job burnout were 22.65 (7.67), 3.85 (4.21) and 1.88 (1.03), respectively. (2) The perceived stress score, mental health score and job burnout score of healthcare workers were positively correlated (r = 0.543–0.699, p