Objective: Exploration of the relationship between mental health constructs and physical health constructs can help practitioners better understand the mental health of vulnerable populations, such as college students in the United States. The purpose of this exploratory study was to investigate the connection between mental well-being and health literacy of US college students. Participants: The sample included 410 undergraduate students (63% white; 71% female) attending universities across the United States. Methods: Participants completed the All Aspects of Health Literacy Scale and the Warwick-Edinburgh Mental Well-being Scale. Univariate and bivariate statistics were observed for all study variables, and three linear regression models were run to see whether functional, communicative, and/or critical health literacy scores predicted mental well-being. Conclusions: Findings suggest that health literacy was associated with improved mental well-being among US college students, which has implications for health programming at US universities, such as the coordination of physical and mental healthcare.