Regular physical activity minimizes the deleterious effects of stress on the body and mind to protect against stress-related mental health issues. Regular physical activity also promotes mindfulness—a mental state of non-judgmental, present-oriented attention, and this may further augment the mental health benefits of being physically active. The present study examined the role of mindfulness as a moderator of the association between physical activity and stress reactivity. Sedentary and recreationally active university students (N = 28) completed questionnaires of physical activity, mindfulness, and mental health. We experimentally induced a stress response using the Trier Social Stress Test (TSST) and measured its impact on physiological (heart rate) and psychological (state anxiety) reactivity. Participants were stratified by physical activity level and by mindfulness for subsequent analyses. Preliminary results reveal that highly active participants were more mindful than their less active counterparts (p = 0.02). They also had lower physiological stress reactivity to the TSST, as indicated by lower maximum and average heart rates (p < 0.01). Moreover, participants who were both highly active and highly mindful exhibited less depression (p = 0.004), anxiety (p = 0.03), and stress (p = 0.01), and experienced less psychological stress reactivity to the TSST, as indicated by trends toward lower state anxiety before, during, and after the stressor. The results suggest that mindfulness may moderate the association between physical activity and stress reactivity, and point to the promise of interventions that combine physical activity and mindfulness training to reduce stress and improve mental health.