Ethnic differences in central sensitization of pain processing and stress-relevant endogenous pain regulatory mechanisms were examined. Forty-four African Americans (AAs; 50% women) and 44 non-Hispanic Whites (nHWs; 50% women) matched for socioeconomic status, were tested for pain responses to the temporal summation of heat pulses and ischemic and cold pain. Resting and stress blood pressure (BP) and norepinephrine (NE) were assessed. AAs had heightened pain responses to all 3 pain tasks relative to nHWs. In nHWs, higher BP and NE were related to reduced pain. In AAs, there was no relationship between BP and pain, but higher NE was related to increased pain. This study provides evidence for ethnic differences in centrally mediated pain and extends prior research demonstrating ethnic differences in endogenous pain regulatory mechanisms. These results have implications for understanding biobehavioral factors contributing to ethnic disparities in clinical pain.