We evaluated the influence of population size (POP), HDI (Human Development Index) and GDP (gross domestic product) on the COVID-19 pandemic in the Southeast region of Brazil, between February 2020 and May 2021. Methods: Cases, deaths, incidence coefficient, mortality rate and lethality rate were compared among states. The cities were divided into strata according to POP, GDP, and HDI. Data were compared by Welch’s ANOVA, nonlinear polynomial regression, and Spearman’s correlation test (rS). Results: The highest incidence coefficient (p < 0.0001) and mortality rate (p < 0.05) were observed in the states of Espírito Santo and Rio de Janeiro, respectively. Until the 45th week, the higher the POP, the higher the mortality rate (p < 0.01), with no differences in the remaining period (p > 0.05). There was a strong positive correlation between POP size and the number of cases (rS = 0.92, p < 0.0001) and deaths (rS = 0.88, p < 0.0001). The incidence coefficient and mortality rate were lower (p < 0.0001) for low GDP cities. Both coefficients were higher in high- and very high HDI cities (p < 0.0001). The lethality rate was higher in the state of Rio de Janeiro (p < 0.0001), in large cities (p < 0.0001), in cities with medium GDP (p < 0.0001), and in those with high HDI (p < 0.05). Conclusions: Both incidence and mortality were affected by time, with minimal influence of POP, GDP and HDI.