Objectives: Although several factors are known to contribute to ethnic differences in pain, relatively little attention has been devoted to physiological factors. Our first aim was to examine the relationship between cortisol and pain responses during a coldpressor task (CPT) among African American (AA) and nonHispanic White (NHW) adults with knee osteoarthritis (OA). Our second aim was to assess the relationship between perceived racial discrimination and cortisol among AA participants. Materials and Methods: Participants were 91 (56 AA; 35 NHW) community-dwelling adults between the ages of 45 to 85 with knee OA based upon the American College of Rheumatology clinical criteria. Plasma cortisol was measured at 3 timepoints: (1) baseline, (2) before the CPT, and (3) 20 minutes following the CPT. Perceived racial discrimination was measured by the Experiences of Discrimination scale. Results: Using linear regression, we found a significant interaction between ethnicity and cortisol before the CPT with pain intensity ratings (b = 0.26; P= 0.02). Analysis of simple slopes revealed that cortisol concentrations were negatively associated with pain intensity ratings in NHW participants (b= 0.54; P= 0.001), but not in AA participants (b = 0.15; P= 0.26). Perceived racial discrimination was not related to cortisol concentrations or pain ratings. Discussion: Consistent with previous findings in young healthy adults, cold-pressor pain responses are related to pre-CPT cortisol concentrations in NHW persons with knee OA but not in their AA counterparts. Additional studies are required to better understand this finding.