This study aims to determine the impact of the COVID-19 pandemic, specifically considering the mandatory social isolation measures implemented, on the perceived stress of a sample of dentists and dental students from Latin America and the Caribbean, as well as the associated sociodemographic and pandemic-related variables. A cross-sectional survey was conducted with a sample of 2036 dentists and dental students (1433 women). For the main outcome, the 14-item Perceived Stress Scale (PSS-14) was used. The survey also questioned sociodemographic aspects, questions on the COVID-19 pandemic, health variables, and habits. Descriptive, bivariate, and multivariate analyses (linear regression) were applied to observe the factors associated with perceived stress. The PSS-14 mean score was 24.76 (±11.76). Hierarchical regression models showed significant variables associated with the PSS-14 scores: income level during mandatory social isolation, having older adults under care during mandatory social isolation, self-perceived level of concern regarding COVID-19, self-perceived health, Coffee consumption during mandatory social isolation. In general terms, the pandemic has influenced the personal, social, labor, and everyday life of dental staff and affected the mental health of this population specifically when perceived stress is considered. Public policies, strategies, and mental health surveillance systems are required for this population.