ABSTRACT Objective This study aimed to estimate the prevalence of alterations in the self-perception of mental health (SpMH) during the COVID-19 pandemic and their associated factors in four Latin American countries. Methods: A cross-sectional study of data collected from adults in 2021 through the McDonnell Collaborative COVID-19 Response Survey. The sample was composed by 8125 people from Brazil, Colombia, Mexico, and Chile. A generalized linear model (GLM) for a binary outcome variable with a logistic link and fixed country effects was used. Results: There were 2336 (28.75%) people who considered having suffered alterations in SpMH. The unemployed [OR: 1.40 (95% CI: 1.24–1.58)], those with bad/regular quality of life [OR: 5.03 (95% CI: 4.01-6.31)], and those with high socioeconomic status (SES) [OR: 1.66 (95% CI: 1.41–1.96)] had a higher risk of SpMH alterations than those with full-time employment, excellent quality, and low SES status. According to the fixed-effects model, Brazilians living in the country during the pandemic, who disagreed with their government’s decisions [OR: 2.05 (95%CI: 1.74–2.42)] and lacked trust in their government [OR: 2.10 (95%CI: 1.74–2.42)] had a higher risk of having SpMH alterations. Conclusion: Nearly 30.0% of respondents indicated that the COVID-19 pandemic altered their SpMH. This outcome was associated with political, sociodemographic, and health risk factors. These findings should help policymakers develop post-pandemic community interventions.