Hostile conflict in marriage can increase risks for disease and mortality. Physiological synchrony between partners-e.g., the linkage between their autonomic fluctuations-appears to capture engagement, or an inability to disengage from an exchange, and thus may amplify the health risks of noxious interactions such as marital conflict. Prior work has not examined the unique health correlates of this physiological signature. To test associations between couples’ heart rate variability (HRV) synchrony during conflict and inflammation, 43 married couples engaged in a marital problem discussion while wearing heart monitors and provided four blood samples; they repeated this protocol at a second visit. When couples’ moment-to-moment HRV changes tracked more closely together during conflict, they had higher levels of three inflammatory markers (i.e., IL-6, stimulated TNF-α, and sVCAM-1) across the day. Stronger HRV synchrony during conflict also predicted greater negative affect reactivity. Synchrony varied within couples, and was related to situational factors rather than global relationship traits. These data highlight partners’ HRV linkage during conflict as a novel social-biological pathway to inflammation-related disease.