Introduction: This study examines the protective effects of variables of dispositional optimism and creativity with respect to measurements of psychopathology or psychological distress. Method: A total of 113 university students from different degree programs participated in the research. Measures of creativity (CREA), optimism (LOT-R) and psychopathological symptoms (SCL-90) were administered during their course on public speaking. Correlational and regression analyses were carried out using optimism and creativity as predictors for psychopathological symptoms. In order to round out the analysis, ANOVAS were carried out between three levels of creativity, with groups formed according to low, medium and high creativity. Results: Strong negative correlations, statistically significant, were found between dispositional optimism and psychopathological symptoms. The psychopathological symptoms measured by the SCL-90 were explained by the variable of dispositional optimism, primarily in its dimensions of depression and interpersonal difficulties. However, no significant correlational relationship was found between creativity and the measure of psychopathology. Differences in psychopathological symptoms, however, were found according to the three groups of creativity; participants with a medium level of creativity showed the least psychopathological symptoms. Discussion and Conclusions: In the light of the results of this study, the protective effect of optimism against psychopathology, as found in other studies, was confirmed, and we offer specific proposals to be applied in psychological well-being programs. Various possibilities are suggested to explain the relationship found between creativity and psychopathology. (Contains 6 tables.)