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BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented challenge for public health and has caused the loss of millions of lives worldwide. Hospital workers play a key role in averting the collapse of the health system, but the mental health of many has deteriorated during the pandemic. Few studies have been devoted to identifying the needs of workers on frontline duty. AIM To investigate dimensions of common emotional symptoms and associated predictors among Brazilian workers in a COVID-19 reference hospital. METHODS This is an observational study of the mental health of professionals in a COVID-19 hospital in the city of São Paulo. We invited all hospital employees to respond to an online survey between July and August 2020, during the first peak of the pandemic. Data of 1000 participants who completed the survey were analyzed (83.9% were women and 34.3% were aged 30 to 40). Hospital workers self-reported the presence of symptoms of depression, anxiety, trauma-related stress, and burnout through the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Impact of Event Scale-Revised and the Mini-Z Burnout Assessment respectively. Responses were assembled and subjected to exploratory factor analysis to reveal workers’ core emotional distress. Multiple linear regression models were subsequently carried out to estimate the likelihood of dimensions of distress using questions on personal motivation, threatening events, and institutional support. RESULTS Around one in three participants in our sample scored above the threshold of depression, anxiety, post-traumatic stress disorder, and burnout. The factor analysis revealed a three-factor structure that explained 58% of the total data variance. Core distressing emotional domains were avoidance and re-experience, depression-anxiety, and sleep changes. Regression analysis revealed that institutional support was a significant protective factor for each of these dimensions (β range = -0.41 to -0.20, P < 0.001). However, participants’ personal motivation to work in healthcare service was not associated with these emotional domains. Moreover, the likelihood of presenting the avoidance and re-experience dimension was associated with having a family member or close friend be hospitalized or die due to COVID-19 and having faced an ethical conflict. CONCLUSION Distressing emotional domains among hospital workers were avoidance and re-experience, depression and anxiety, and sleep changes. Improving working conditions through institutional support could protect hospital workers' mental health during devastating public health crises.