The present study was designed to investigate the relationship among physiologic concordance, patient-perceived therapist empathy, and social-emotional process during psychotherapy. Simultaneous measures of skin conductance (SC) were obtained from 20 unique and established patient-therapist dyads during a live therapy session followed by patient ratings of therapist empathy. Paired SC data of hypothetical dyads were used to test the reliability of the proposed measure of SC concordance. Observer microanalyses of social-emotional process were used to compare short segments of high versus low physiologic concordance. Results show a significant positive correlation (r = 0.47, p = 0.03) between SC concordance and patient ratings of perceived therapist empathy. Microanalyses suggest that during moments of high versus low SC concordance, there were significantly more positive social-emotional interactions for both patients and therapists (p = 0.01). The results support a biological model of perceived patient empathy and patient-therapist social-emotional process during psychotherapy.