As the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic contin-ues to expand, healthcare resources globally have been spread thin. Now, the disease is rapidly spreading across South America, with deadly consequences in areas with already weakened public health systems. The Amazon region is particularly susceptible to the wide-spread devastation from Coronavirus disease 2019 (COVID-19) because of its immunologi-cally fragile native Amerindian inhabitants and epidemiologic vulnerabilities. Herein, we discuss the current situation and potential impact of COVID-19 in the Amazon region and how further spread of the epidemic wave could prove devastating for many Amerindian people living in the Amazon rainforest.