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Objectives: To assess occupational burnout (OB) changes among Brazilian healthcare workers (HCWs) from COVID-19 onset to six months later (T1) and identify risk and protective factors., Methods: Using the Copenhagen Burnout Inventory and hierarchical multivariate linear regression in a two-stage online survey (initial n = 1,054; T1 n = 316), this study examined the impact of various factors on OB., Results: Significant increases in personal and work-related OB were observed by T1. Psychiatric diagnosis and workload emerged as risk factors (p < 0.01), while having a partner, good family relations, workplace well-being, and adequate sleep were protective (p < 0.001)., Conclusions: OB levels among Brazilian HCWs increased during the COVID-19 pandemic. Interventions should target personal and organizational wellness to alleviate burnout, emphasizing the importance of strong relationships, workplace health, and good sleep practices., Competing Interests: Conflict of interest for all authors: None declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)