Abstract Interpersonal touch and social support can influence physical health, mental well-being and pain. However, the mechanisms by which supportive touch promotes analgesia are not well understood. In Study 1, we tested how three kinds of social support from a romantic partner (passive presence, gentle stroking and handholding) affect pain ratings and skin conductance responses (SCRs). Overall, support reduced pain ratings in women, but not men, relative to baseline. Support decreased pain-related SCRs in both women and men. Though there were no significant differences across the three support conditions, effects were largest during handholding. Handholding also reduced SCRs in the supportive partner. Additionally, synchronicity in couples’ SCR was correlated with reductions in self-reported pain, and individual differences in synchrony were correlated with the partner’s trait empathy. In Study 2, we re-analyzed an existing dataset to explore fMRI activity related to individual differences in handholding analgesia effects in women. Increased activity in a distributed set of brain regions, including valuation-encoding frontostriatal areas, was correlated with lower pain ratings. These results may suggest that social support can reduce pain by changing the value of nociceptive signals. This reduction may be moderated by interpersonal synchrony and relationship dynamics.