Brazil had the second-largest death toll during the COVID-19 pandemic, with indigenous peoples disproportionately affected among ethnic groups. Parallel to the pandemic, Brazil has recorded the highest rate of deforestation globally, with encroachments into Indigenous territories putting climate stabilization and biodiversity at risk. However, the effects of deforestation on COVID-19 transmission to Brazil’s Indigenous peoples are unknown. This study shows that during the pre-vaccination period, deforestation partially explains COVID-19 transmission among Indigenous populations. Our main results for the pre-vaccination period indicate that a daily increase in deforestation per km ² is associated, on average, with the confirmation of 0.76 (p < 0.004, 95% CI: 0.240 - 1.276) new daily cases of COVID-19 among Indigenous peoples 14 days after deforestation warnings. Our estimates suggest deforestation explains at least 9.6% of all COVID-19 cases among indigenous populations. The association between the two variables disappears after the vaccination program. Our findings provide empirical evidence on the interplay between environmental degradation and negative health outcomes in a vulnerable segment of society in the context of a pandemic. Furthermore, these findings highlight the importance of the One Health approach to building preparedness for future pandemic threats.