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Abstract Objective Coronavirus disease 2019 (COVID-19) was declared a global pandemic early in 2020, followed by a period during which governments imposed strict social distancing measures to slow transmission. However, most essential services remained open, and those working in offices faced a higher risk of infection compared to those working at home. We compare the occurrence and potential determinants of mental health outcomes, functioning, and quality of life (QoL) in a subset of a sample of Brazilian individuals who worked from home and a subset who worked in the office during the first wave of COVID-19. Methods Data were collected during the first wave of COVID-19, using an online survey to assess sociodemographic and clinical variables, functioning with the Digital Functioning Assessment Short Test (D-FAST), QoL with the European Health Interview Surveys QoL instrument (EUROHIS-QOL), depression with the Patient-Reported Outcomes Measurement Information System (PROMIS) depression instrument, anxiety with the PROMIS anxiety instrument, and stress symptoms with the Impact of Event Scale-Revised (IES-R) in a large sample comprising individuals who worked in offices (n = 1685) or worked from home (n = 1,338). Results Analysis revealed that depressive and post-traumatic stress symptoms were less prevalent in individuals who worked from home and showed that they had higher functioning and QoL than those working in the office. Individuals who worked in the office were younger, more likely to be female, had lower household income, had low educational level, and were more likely to be unmarried than the home working group. Conclusion Our findings support the notion of the negative impact of the COVID-19 pandemic on mental health in both office workers and those working from home. However, the group who worked from home seem to be more resilient with fewer psychiatric symptoms and better functioning. 201 COVID19 COVID 19 (COVID-19 2020 transmission However open outcomes (QoL COVID19. 19. COVID19, 19, variables DFAST, DFAST D FAST , (D-FAST) EUROHISQOL, EUROHISQOL EUROHIS QOL (EUROHIS-QOL) PatientReported Patient Reported (PROMIS ScaleRevised Scale Revised IESR IES R (IES-R n 1685 1,338. 1338 1,338 . 1 338 1,338) posttraumatic post traumatic younger female income level COVID-1 20 COVID1 (COVID-1 202 (D-FAST (EUROHIS-QOL 168 133 1,33 33 COVID- 2 (COVID- 16 13 1,3 3 (COVID 1,