The continual expansion of developmental frontiers has impacted dramatically upon Indigenous health in Brazil. When the COVID-19 pandemic struck in Mato Grosso do Sul, its Indigenous populations were already living in circumstances of environmental degradation, food insecurity, racism, and structural violence. The synergistic interaction between the SARS-CoV-2 virus, other pathogens, and biosocial factors resulted in what Singer (2010) terms as ‘syndemics’. In the case of Mato Grosso do Sul, it brought about a substantial increase in the disease burden of Indigenous Peoples, where child malnutrition, obesity, hypertension, respiratory and parasitic diseases, and maternal mortality appear at higher rates than in the non-Indigenous population. This Research Article discusses the coping and participatory strategies that were employed by Indigenous Peoples early in the pandemic. Efforts by Indigenous Peoples to address the pandemic reveal ‘a clash’ between Indigenous and Colonial cosmographies with regard to notions of the body and health. Considering the Indigenous perspective on the relation between territoriality and health, the analysis highlights asymmetries of power and embodied vulnerabilities and the limits of the Anthropocene as a global perspective.