A number of experts have described mindfulness as a naturally occurring quality in the human mind that is present to some degree in all people, even without training in mindfulness or meditation. This study examined whether trait mindfulness is associated with reduced stress response activation and enhanced self-regulatory activity with recurrent stress. Self-ratings of mindfulness and continuous measures of physiological reactivity before, during, and after an interview about a recurrent stressful issue were collected from 47 undergraduate participants to examine our primary objective. Findings indicated that mindful individuals were less likely to engage in metabolically costly physiological activation in response to an emotionally challenging task, but were more likely to engage parasympathetic responding following the task, a response which is associated with effective downregulation following stress. Results from our study suggest that “natively mindful” individuals have the ability to engage self-regulatory physiological responding associated with improved adaptability and flexibility in a changing environment. Thus, mindfulness may be associated with physical indices of emotional well-being. Furthermore, our data adds evidence for the validity of self-report measures of mindfulness.