Background: Peru had the highest COVID-19 accumulated mortality rate worldwide. A greater disadvantage in the population infected with COVID-19 living under chronic hypoxia would be expected. However, previous studies reported a lower mortality at higher altitudes. Aims and objectives: Assess the relationship between altitude and COVID-19 mortality rate and case incidence in Peru at a district level from March 6th, 2020, to February 28th, 2022, and in its 3 waves. Methods: Ecological analytic study examining open data. 1874 Peruvian districts, ranging from 3 to 4675 meters (m), with 3 372 962 COVD-19 cases and 212 017 deaths were analyzed. Correlation statistics and a multivariate linear regression model were used to assess this relationship in this time period and in 3 arbitrarily defined waves. Results: A negative coefficient of -0.00012 (95% CI -0.00015 to -0.00008) between altitude and mortality rate during the pandemic was obtained, corresponding to a 5.82% mortality decrease for every 500 m. Similar findings for the 3 waves were observed, the first one with -0.000142 (95% CI -0.000178 to -0.000106); the second one, -0.000071 (95% CI -0.000101 to -0.000041); and the third one, -0.000017 (95% CI -0.000027 to -0.000006), equivalent to a 6.76%, 3.49% and 0.85% mortality decrease for every 500 m. A coefficient of -0.0000905 (95% CI -0.000134 to -0.000047) between altitude and case incidence was observed, meaning a 4.42% decrease for every 500 m. In the second and third wave, a 5.08% and 3.92% incidence decrease was found for every 500 m. Conclusions: Altitude had a protective effect against COVID-19 mortality rate and case incidence in Peru.