Objective Informed by the contextual behavioral science (CBS) model of behavioral health, the present cross-sectional study examined whether mindful awareness moderated the associations between psychological inflexibility and four distress variables. Participants Cross-sectional data were collected from 402 ethnically diverse undergraduate college students from September 2015 to October 2015. Methods Participants competed an online self-report survey. Results Mindful awareness moderated the associations between psychological inflexibility and distress variables, with stronger associations for somatization and anxiety, and weaker associations for general distress and depression. Specifically, the strength of the positive associations between psychological inflexibility and these distress variables were substantially greater among those low in mindful awareness. Conclusion These findings suggest that a greater degree of mindful awareness may buffer the effects of psychological inflexibility on distress variables, particularly somatization and anxiety. Theoretical and applied implications as well as limitations of the study are discussed.