The aim of the study was to investigate whether simple guided mindfulness practices in a relationship enrichment program would lead spouses to experience physiological relaxation. Skin conductance and cardiac activity were recorded from ten healthy couples (N = 20 clients) twice during 90-min relationship enrichment sessions. To assess the usefulness of mindfulness exercises for couple therapy practices, different types of phases in a semi-structured setting were applied in the sessions: (i) phases evoking positive valence, (ii) challenging phases inducing stress, and (iii) mindfulness phases inducing relaxation. It was found that the spouses showed significant physiological relaxation, marked by decreases in skin conductance and increases in respiratory sinus arrhythmia, only during the mindfulness periods. However, the effects of mindfulness were not long-lasting, since the autonomic nervous system activity of most of the participants returned to baseline values soon after the exercises. No differences were observed between the cognitive and body-oriented mindfulness exercises in the amount of physiological relaxation.