Thomson, Timothy M., Fresia Casas, Harold Andre Guerrero, Rómulo Figueroa-Mujíca, Francisco C. Villafuerte, and Claudia Machicado. Potential protective effect from COVID-19 conferred by altitude A longitudinal analysis in Peru during full lockdown. High Alt Med Biol. 22 209-224, 2021. Background The COVID-19 pandemic had a delayed onset in America. Despite the time advantage for the implementation of preventative measures to contain its spread, the pandemic followed growth rates that paralleled those observed before in Europe. Objectives To analyze the temporal and geographical distribution of the COVID-19 pandemic at district-level in Perú during the full lockdown period in 2020. Methods Analysis of publicly available data sets, stratified by altitude and geographical localization. Correlation tests of COVID-19 case and death rates to population prevalence of comorbidities. Results We observe a strong protective effect of altitude from COVID-19 mortality in populations located above 2,500 m. We provide evidence that internal migration through a specific land route is a significant factor progressively overriding the protection from COVID-19 afforded by high altitude. This protection is independent of poverty indexes and is inversely correlated with the prevalence of hypertension and hypercholesterolemia. Discussion Long-term adaptation to residency at high altitude may be the third general protective factor from COVID-19 severity and death, after young age and female sex. Multisystemic adaptive traits or acclimatization processes in response to chronic hypobaric hypoxia may explain the apparent protective effect of high altitude from COVID-19 death.