Purpose: Research indicates pain-related disparities in the impact of knee osteoarthritis (OA) across both sex and ethnicity/race. While several factors likely contribute to these disparities, experiences of discrimination are associated with poor OA-related pain, disability, and functional performance. However, the mechanisms that mediate experiences of discrimination and OA-related outcomes are unclear. The current cross-sectional study examined the associations between everyday experiences of discrimination and clinical pain, disability and functional performance among non-Hispanic Black (NHB) and non-Hispanic White (NHW) persons with or at risk of knee OA and assessed the serial mediated model of perceived stress and pain catastrophizing on these relation-ships in women only. Patients and Methods: Participants were 188 community-dwelling adults who presented with unilateral or bilateral knee pain and screened positive for clinical knee pain. Participants completed several measures including experiences of discrimination, Perceived Stress Scale, Coping Strategies Questionnaire-Revised (CSQ-R): Pain Catastrophizing subscale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Graded Chronic Pain Scale (GCPS), and Short Physical Performance Battery (SPPB). Results: As compared to NHW participants, NHB individuals reported experiencing significantly higher levels of discrimination (F(1, 175)=26.660, p<0.001), greater levels of pain catastrophizing (F(1, 180)=12.919, p<0.001), higher levels of clinical pain and disability, and lower levels of physical function (ps<0.05). However, perceived stress was positively corre-lated with discrimination in the NHW group only (NHW females: r=0.40, p<0.01; NHW males: r=0.37, p<0.05). Further, perceived stress and pain catastrophizing mediated the relationship between discrimination and outcome variables (WOMAC pain, GCPS interference [pain disability], and SPPB function) in female participants after controlling for relevant sociodemographic variables (study site, age, race, income, and body mass index). Conclusion: These results may have implications for the treatment of perceived stress and catastrophizing as a means to reduce the negative impact of experiences of discrimination on the experience of chronic pain, particularly for women.