COVID-19 is spreading rapidly in Brazil, a country of continental dimensions, but the incidence of the disease is showing to be very heterogeneous, affecting cities and regions differently. Thus, there is a gap regarding what factors would contribute to accentuate the differences in the incidence of COVID-19 among Brazilian cities. This work aimed to evaluate the effect of altitude on the incidence of COVID-19 in Brazilian cities. We analyzed the relative incidence (RI), the relative death rate (RDR) of COVID-19, and air relative humidity (RH) in all 154 cities in Brazil with a population above 200 thousand inhabitants, located between 5 and 1135 m in altitude. Pearson's correlation analysis was performed to compare a relationship between altitude with RI and RDR, and between RH with RI and RDR. Altitudes were classified into three classes [low (altitude ≤ 97 m a. s. l), middle (97 < altitude ≤ 795 m a. s. l), high (795 < altitude ≤ 1135 m a. s. l)] for the RI, RDR, and RH variables. To compare the three classes of altitude, analysis of variance (ANOVA) and Tukey test were used to compare averages (p < 0.05). Our epidemiological analysis found that the RI, RDR, and RH were lower in cities located in high altitudes (795 < altitude ≤ 1135 m a. s. l) when compared to the middle (97 < altitude ≤ 795 m a. s. l) and low (altitude ≤ 97 m a. s. l) cities altitudes. Furthermore, our study shows that there is a negative correlation between the incidence of COVID-19 with altitude and a positive correlation with RH in the cities analyzed. Brazilian cities with high altitude and low RH have lower RI and RDR from COVID-19. Thus, high altitude cities may be favorable to shelter people at risk. This study may be useful for understanding the behavior of SARS-CoV2, and start point for future studies to establish causality of environmental conditions with SARS-CoV2 contributing to the implementation of measures to prevent and control the spread of COVID-19.