The objective of this study was to examine the role resilience plays in the relationship between the Big Five personality traits and anxiety and life satisfaction. A total of 470 students from the University of Zagreb in Croatia participated in the study. The results are explained within the framework of McCrae and Costa's (1991) temperament and instrumental model of personality and well-being. A path analysis and a bootstrapping resampling method were performed. Higher levels of extraversion, agreeableness, conscientiousness, and emotional stability were associated with higher levels of resilience, which was related to lower levels of anxiety and higher life satisfaction. It can be concluded that resilience is a full mediator between extraversion and conscientiousness on the one hand, and life satisfaction and anxiety on the other. In addition, resilience is a partial mediator between agreeableness and emotional stability, and also between life satisfaction and anxiety. The practical contribution of the study lies in understanding how to better support students' mental health by targeting the protective factors of different personality traits.