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Objective: To compare the mortality rates from COVID-19 among indigenous populations of the Amazon and Andean regions of Peru during the years 2020, 2021 and 2022., Methods: Secondary analysis of 33,567 data from the COVID-19 Notification System of the National Epidemiology Center, Prevention and Control of Diseases (CDC-Peru), from the years 2020-2022. The variables were age, sex, belonging to the Andean or Amazonian ethnic group, number and type of symptoms and risk conditions, abnormal findings in chest X-rays, year of data collection for hospitalization and death from COVID-19. Poisson family generalized linear regression models with logarithmic linkage and robust variance were used to establish differences in mortality between ethnic groups. Crude and adjusted risk ratio (RR) with 95 % confidence intervals (CI) were calculated., Results: 33,567 participants with an average age of 33.6 years were included, 44.4 % were men and 70.2 % belonged to the Amazonian ethnic group. Most of those affected by COVID-19 presented 2 symptoms (38.8 %), 4.8 % presented some risk condition, 1451 (4.3 %) were hospitalized, and 433 (1.3 %) died. The adjusted analysis showed that the Andean group, compared to the Amazonian, tended to have a higher probability of death, and this association was statistically significant, RR =7.6, 95 % CI (5.5-10.5)., Conclusions: Patients from Andean indigenous communities had an almost 8 times higher risk of death from COVID-19., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)