ObjectiveTo examine the SARS-CoV-2 infection rate in a cohort of 6500 professional athletes and staff during the 2020 football (soccer) season in São Paulo, Brazil.MethodsThis retrospective cohort study included 4269 players (87% male, age: 21.7±4.2 years) and 2231 staff (87% male, age: 42.6±11.9 years) from 122 teams (women: n=16) involved in eight leagues (women: n=2), which took place in São Paulo, Brazil. Between 4 July 2020 and 21 December 2020, swab samples were collected weekly (n=29 507) and tested for SARS-Cov-2 via reverse transcription-PCR by an accredited laboratory commissioned by the São Paulo Football Federation. We contacted the medical staff of each team with positive cases to collect information on disease severity.ResultsAmong 662 PCR-confirmed cases, 501 were athletes and 161 were staff. The new infection rate was 11.7% and 7.2% for athletes and staff, respectively. Athletes were more susceptible to infection than staff (OR: 1.71, 95% CI: 1.42, 2.06, p<0.001), although with lower chance for moderate to severe disease (OR: 0.06, 95% CI: 0.01, 0.54, p=0.012). Six teams had ≥20 individuals testing positive for SARS-CoV-2, whereas 19 teams had ≥10 confirmed cases. Twenty-five mass outbreaks were identified (≥5 infections within a team in a 2-week period). The prevalence of SARS-CoV-2 infections was similar in athletes and staff as the general population in São Paulo.ConclusionDespite weekly testing and other preventive measures, we found a high SARS-CoV-2 infection rate in athletes and staff after resuming football, which coincides with the high prevalence of infection in the community during the same period. These data may assist policy-makers and sports federations for determining if and when it is safe to resume competitions.