Ortiz-Prado, Esteban, Raul Patricio Fernandez Naranjo, Eduardo Vasconez, Katherine Simbaña-Rivera, Trigomar Correa-Sancho, Alex Lister, Manuel Calvopiña, and Ginés Viscor. Analysis of excess mortality data at different altitudes during the COVID-19 outbreak in Ecuador. . 22:406-416, 2021. It has been speculated that living at high altitude confers some risk reduction in terms of SARS-CoV-2 infection, reduced transmissibility, and arguable lower COVID-19-related mortality. We aim to determine the number of excess deaths reported in Ecuador during the first year of the COVID-19 pandemic in relation to different altitude categories among 221 cantons in Ecuador, ranging from sea level to 4,300 m above. A descriptive ecological country-wide analysis of the excess mortality in Ecuador was performed since March 1, 2020, to March 1, 2021. Every canton was categorized as lower (for altitudes 2,500 m or less) or higher (for altitudes >2,500 m) in a first broad classification, as well as in two different classifications: The one proposed by Imray et al. in 2011 (low altitude <1,500 m, moderate altitude 1,500-2,500 m, high altitude 2,500-3,500 m, or very high altitude 3,500-5,500 m) and the one proposed by Bärtsch et al. in 2008 (near sea level 0-500 m, low altitude 500-2,000 m, moderate altitude 2,000-3,000 m, high altitude 3,000-5,500 m, and extreme altitude 5,500 m). A Poisson fitting analysis was used to identify trends on officially recorded all-caused deaths and those attributed to COVID-19. In Ecuador, at least 120,573 deaths were recorded during the first year of the pandemic, from which 42,453 were catalogued as excessive when compared with the past 3 years of averages (2017-2019). The mortality rate at the lower altitude was 301/100,000 people, in comparison to 242/100,000 inhabitants in elevated cantons. Considering the four elevation categories, the highest excess deaths came from towns located at low altitude (324/100,000), in contrast to the moderate altitude (171/100,000), high-altitude (249/100,000), and very high-altitude (153/100,000) groups. This is the first report on COVID-19 excess mortality in a high-altitude range from 0 to 4,300 m above sea level. We found that absolute COVID-19-related excess mortality is lower both in time and in proportion in the cantons located at high and very high altitude when compared with those cantons located at low altitude.