question: Objective Explore the factors that could explain the differences of fatality rates among indigenous groups with COVID-19 diagnosis compared to the rest of the population in Mexico. Study design We analyzed the public data of COVID-19 surveillance, of the Mexican Ministry of Health, to estimate COVID-19 fatality rates by ethnicity. Methods ﻿ We explored associated factors using Cox proportional hazards models stratified by outpatient and hospital management at diagnosis; analysis was conducted in three scenarios: national level, states with 89% of indigenous population, and South Pacific region. Results 412,017 COVID-19 cases were included, with 1.1% of indigenous population. Crude fatality rate per 1,000 person-weeks was 64.8% higher among indigenous than in non-indigenous (29.97 vs. 18.18, respectively), and it increased more than twice within outpatients (5.99 vs. 2.64). Cox analysis revealed that indigenous with outpatient management had higher fatality rate compared to non-indigenous outpatients; at national level (HR 1.63 95% CI 1.34-1.98), within the subgroup of 13 states (HR 1.66 95% CI 1.33-2.07), and South Pacific region (HR 2.35 95% CI 1.49-3.69). Factors associated with higher fatality rates among non-indigenous and indigenous outpatients were age, sex and comorbidities. Conclusions COVID-19 fatality is higher among indigenous populations, particularly within cases managed as outpatients.