Mindfulness has been associated with better psychological and physical health; although, the mechanisms of these benefits are poorly understood. We explored the role of mindfulness in stress-health pathways among undergraduates at a large public university. Participants reported on demographic and academic variables and completed data collection at two time points during the academic semester, approximately one month apart. At each collection, measures of mindfulness, perceived stress, and psychological well-being were gathered. Students provided two days of home-based saliva collection for assessment of cortisol. Mean scores were computed for each of the measures, over the two assessments. Hierarchical multiple regressions adjusting for GPA, hours of paid employment per week, minority status, and living situation explored the impact of mindfulness in our stress-health model. Students with higher dispositional mindfulness reported significantly less perceived stress and had lower overall mean diurnal cortisol. Mindfulness was associated with greater psychological well-being. Exploratory analyses suggested that future research should explore the potential mediating or moderating relationships between mindfulness, perceived stress, and cortisol. Findings suggest that mindfulness may help attenuate both psychological and physiological stress responses to college stress.