The human ability to synchronize with other individuals is critical for the development of social behavior. Recent research has shown that physiological inter-personal synchronization may underlie behavioral synchrony. Nevertheless, the factors that modulate physiological coupling are still largely unknown. Here we suggest that social touch and empathy for pain may enhance interpersonal physiological coupling. Twenty-two romantic couples were assigned the roles of target (pain receiver) and observer (pain observer) under pain/no-pain and touch/no-touch conditions, and their ECG and respiration rates were recorded. The results indicate that the partner touch increased interpersonal respiration coupling under both pain and no-pain conditions and increased heart rate coupling under pain conditions. In addition, physiological coupling was diminished by pain in the absence of the partner's touch. Critically, we found that high partner's empathy and high levels of analgesia enhanced coupling during the partner's touch. Collectively, the evidence indicates that social touch increases interpersonal physiological coupling during pain. Furthermore, the effects of touch on cardio-respiratory inter-partner coupling may contribute to the analgesic effects of touch via the autonomic nervous system.