It has been suggested that it would be more appropriate to term the COVID-19 pandemic a syndemic, as the infection interacts synergistically with pre-existing chronic conditions such as obesity. Both conditions occur with steep socio-economic inequalities, and Brazil is suffering a heavy burden from both. What and who drives the clustering and interaction of these disorders? In this commentary, we examine the pathways leading to the COVID-19 syndemic. Deforestation, declining biodiversity and factory farming are promoting the emergence of new pathogens. Widespread use of pesticides influences immune, endocrine and metabolic systems. The ingestion of ultra-processed food promotes malnutrition and obesity in a country where at the same time poverty and food insecurity is rising. Brazilian agribusiness is focused on the production and global export of agricultural commodities, mainly for animal food and meat production. It is made possible through a combination of expanded land use, with deforestation in Amazonas and other Brazilian biomes, and the intensification of land use and cultivation of genetically modified crops with fertilizers and pesticides. This development is not sustainable for either population health or the environment.