To investigate the cumulative incidence and mortality of COVID-19 and the prevalence of comorbidities such as diabetes, obesity and hypertension in regions with different altitude levels ranging from sea level to high altitude. Methodology: Analytical study in which we correlated secondary data obtained from reports of the Ministry of Health and National Institute for Statistics and Informatic. The cumulative incidence and mortality of COVID-19 in 25 peruvian regions is reported, together with its relationnship with altitude levels during March-July 2020 using Pearsońs correlation. We also aiming to assess the prevalence of diabetes, obesity and hypertension with altitude according to the ENDES 2018 data using Gamma statistics. Results: COVID-19 maintained an inverse correlation with higher rates in the coastal regions and lower rates with increasing altitude in the cumulative incidence (Pearson = −0.8, p < 0.000) and mortality (Pearson = −0.77, p < 0.000), adjusted gender and age. The prevalence of diabetes and obesity showed the same inverse correlation trend with altitude (Gamma p < 0.000) but not hypertension (Gamma p = 0.13) Conclusions: The data in Peru it is suggested that physiological adaptation in a hypoxic environment at high altitude may protect persons from the severe impact of acute infection caused by SARS-CoV-2. The reduction in cumulative incidence and mortality rates with increasing altitude is the main finding. Possible mechanisms such as a decreased expression of angiotensin-converting enzyme 2 (ACE2) and a lower virulence because of a high altitude environment, may explain this epidemiological features. In addition, the lower prevalence of diabetes, obesity and hypertension may establish a protective epidemiology against these disease.