This study investigated the effects of a brief mindfulness intervention on romantic partners’ physiological responses to conflict stress moderated by trait mindfulness. Young adult couples (n = 101 dyads) completed the Five Facet Mindfulness Questionnaire (FFMQ) to assess trait mindfulness approximately 1 week prior to a laboratory session involving a conflict discussion task. One third of partners were randomly assigned to a mindfulness induction condition before the conflict (remaining participants were assigned to a perspective taking or control condition). All participants gave five saliva samples over the course of the session to measure autonomic (salivary alpha-amylase, sAA) and neuroendocrine (cortisol) stress responses. There were no main effects of participation in the mindfulness condition, but analyses revealed differing intervention impacts for partners with high vs. low dispositional mindfulness. According to region of significance testing, partners with high FFMQ scores (top 23 % of men, 12 % of women) showed better stress regulation in the mindfulness condition, i.e., more dynamic sAA reactivity/recovery curves for men and quicker post-stress cortisol recovery for women, whereas those with low FFMQ scores (bottom 5 % of men, 11 % of women) showed poorer regulation, i.e., flatter sAA responses. Implications for using mindfulness to foster stress regulation are discussed.