This study aimed to estimate the prevalence and identify social factors and preventive strategies associated with the coronavirus disease 2019 (COVID-19) in socio and economically vulnerable people (recyclable waste pikers, immigrants/refugees, and homeless people) in Goiânia, Goiás State, Central-Western Brazil. A cross-sectional study was conducted from July 2020 to October 2020. COVID-19 positivity was defined as a positive total anti-SARS-COV-2 antibody test and/or RNA test for SARS-COV-2. Univariable and multiple regression analyses were performed to identify the variables associated with COVID-19. Of the 594 participants, 47.3% were recyclable waste pickers, 29.6% were immigrants/refugees, and 23.1% were homeless people. The positivity for SARS-CoV-2 RNA was 14.1%, whereas for anti-SARS-CoV-2 a total of 30.8% were positive, and 39.4% were positive for at least one COVID-19 marker. Among the 541 individuals, being immigrants/refugees, not wearing a surgical mask, and having three or more people sleeping in the same room were associated with SARS-CoV-2 infection, while using TV news as the main source of information about the pandemic was a protective predictor of COVID-19. This study revealed ethnic and socioeconomic inequalities in the prevalence of COVID-19 among impoverished people in Brazil. Additionally, a high prevalence of COVID-19 was detected in all three groups. Developing new strategies to combat and prevent communicable diseases affecting this population is essential for mitigating future and ongoing pandemics.