To investigate the role of optimism, hope, and gratitude as psychosocial factors for healthy development, especially with regard to anxiety in college students in the context of coronavirus disease 2019 (COVID-19). This is a quantitative, descriptive cross-sectional study. A sociodemographic questionnaire, the Brazilian Gratitude Scale (Escala Brasileira de Gratidão [B-GRAT]), and the Brazilian versions of an anxiety subscale, the Revised Life Orientation Test (LOT-R), Hope Index Scale, and BIG-FIVE were administered. Data were analyzed using the Mann-Whitney U test, the Kruskal-Wallis test, Spearman correlations, and hierarchical linear regression. A total of 297 students were assessed. The relationship between gratitude and anxiety became positive in the hierarchical linear analysis, contradicting the initial negative association between these variables according to the Spearman coefficients. This contradiction may be a result of the suppression effect. When gratitude was added to the model, these three variables together accounted for 38% of the variance in anxiety. This indicates that optimism, hope, and gratitude together are significant predictors, although optimism alone accounts for the greater part of the variance in decreased anxiety. The data confirm that family and religiosity are protective factors against mental illness, specifically non-adaptive anxiety. Furthermore, developing optimism as a protective factor makes it possible to experience less anxiety while hope has the potential to provide the individual with multiple pathways to healthy development. This study highlights that gratitude plays a dual role in these relationships as it has the potential to be associated with anxious feelings with likely negative outcomes while at the same time it can drive positive psychosocial factors of optimism and hope, decreasing anxiety.