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Background COVID-19 and obesity are two concurrent, interrelated pandemics that share similarities in their social causes, including racism. It is essential to understand how their characteristics are interrelated and the possible role of obesity in the association between race/skin color and COVID-19 mortality. Thus, we investigated the relationship between race/skin color and COVID-19 mortality and the modifying effect of obesity on this relationship. Methods It is a retrospective cohort study. We analyzed data from 113,737 adults aged ≥ 19 years hospitalized for COVID-19 in Rio Grande do Sul, Brazil, from March 2020 to December 2021. The study outcome was in-hospital COVID-19 mortality. Exposures included race/skin color, analyzed as White, Brown, and Black and as White and Black (Brown + Black), and obesity. Logistic regression models were used to estimate associations adjusted for age, comorbidities, and health care. Results The cumulative incidence of COVID-19 mortality was 33.46% (95% CI 33.18–33.74). Compared with White individuals, Brown and Black individuals were 39% (95% CI 1.28–1.52) and 30% (95% CI 1.20–1.41) more likely to die from COVID-19, respectively. Brown women with obesity had the greatest likelihood of COVID-19 mortality (1.64 [95% CI 1.27–2.13]) compared with all other groups. Conclusions Brown and Black individuals were more likely to die from COVID-19 than White individuals. Obesity was an effect modifier of the association between race/skin color and COVID-19 mortality, increasing the risk of mortality in the group of Brown women, after adjustments.