BACKGROUND: Several nonpharmaceutical interventions, such as masking, were mandated or recommended during the Coronavirus disease 2019 (COVID-19) pandemic. This study's primary objective is to investigate the relationship between population-level mask usage and excess mortality across Europe. METHODS: We collected data on mask usage and other relevant variables from 24 European countries during 2020-2021, a period in which mask policies varied widely across nations, providing an ideal basis for a natural experiment. To assess the association between mask usage and relevant medical and socioeconomic data at the country level, we conducted both bivariate and multivariate regression analyses. Confounding factors were accounted for in the regression models, and numerous sensitivity tests were performed to ensure robustness. RESULTS: Statistically significant correlations were found between mask usage rate and age-adjusted excess mortality in both bivariate (Spearman coefficient = 0.477, p = 0.018) and multivariate (Standardized coefficient = 0.52, p = 0.0012) regressions. Likewise, vaccination rates showed negative and significant bivariate (Spearman coefficient = -0.659, p <
.001) and multivariate (Standardized coefficient = -0.48, p = 0.0016) correlations with age-adjusted excess mortality. CONCLUSIONS: No correlation was observed between mask usage rates and COVID-19 morbidity. However, significant associations were identified between mask usage rates, COVID-19 mortality, and excess deaths. Various hypotheses have been proposed to explain these associations, with thorough consideration given to potential confounders, such as socioeconomic factors and the severity of COVID-19 waves.