Background: Socially vulnerable populations were vastly affected by the COVID-19 pandemic. The pandemic significantly impacted Brazil, pressuring its healthcare system for several months, with high mortality rates, even among the youngest population. Cohort studies combining disease surveillance are essential for understanding virus circulation in the community, surrogates of protection, vaccine effectiveness, and demand for health resources. Methods: Here, we present the protocol for a community-based prospective cohort study in the largest complex of favelas (slums) in Rio de Janeiro, Brazil (Complexo da Maré). The study participants are residents initially recruited during a massive vaccination campaign in the community. Five waves of data collection at approximately six-month intervals were planned. The first two waves have been completed at the time of writing this study protocol, and the third is underway. The protocol comprises interviews, blood sampling, and records linkage with secondary data to enrich the profiles of cohort participants and community information. We will describe COVID-19 seroprevalence, socio-demographic characteristics, and the burden of COVID-19, followed by estimating the association of socioeconomic factors and the burden of disease with seroprevalence. Discussion: The primary aims of the study are to assess COVID-19 clinical, epidemiological and genomic profiles and outcomes in residents from Maré, including vaccine effectiveness, surrogates of immune protection, virus transmission in households, and the overall burden of the pandemic.