The present study aimed to examine the mediational effects of self-compassion and positive affect in the relationship between stress and life satisfaction of South Korean university students. Questionnaires regarding stress, self-compassion, positive affect, and life satisfaction were distributed to 1,087 university students. Structural equation modeling was conducted to confirm the direct and indirect paths between each variable as regards life satisfaction and gender differences. The main results of this study can be summarized as follows. First, the results showed that the partial mediational model best fit the data, and that positive affect and self-compassion had significant partial mediational effects. Second, positive affect and self-compassion both mediated the relationship between university students' stress and life satisfaction. Third, the partial mediational model fit the data well for both male and female students, although gender differences were found in certain paths. The present study is significant in that it provides empirical evidence for the importance of self-compassion and positive affect in interventions for highly stressed university students. The implications and limitations of the present study were also discussed.