Objective To examine self-reported weight discrimination and differences based on race, sex, and BMI in a biracial cohort of community-based middle-aged adults. Design and Methods Participants (3,466, mean age = 50 years, mean BMI = 30 kg/m2) of the Coronary Artery Risk Development in Young Adults (CARDIA) Study who completed the 25-year examination of this epidemiological investigation in 2010-2011 were reported. The sample included normal weight, overweight, and obese participants. CARDIA participants are distributed into four race-sex groups, with about half being African-American and half White. Participants completed a self-reported measure of weight discrimination. Results Among overweight/obese participants, weight discrimination was lowest for White men (12.0%) and highest for White women (30.2%). The adjusted odds ratio (95% CI) for weight discrimination in those with class 2/3 obesity (BMI ≥ 35 kg/m2) versus the normal-weight was most pronounced: African American men, 4.59 (1.71-12.34); African American women, 7.82 (3.57-17.13); White men, 6.99 (2.27-21.49); and White women, 18.60 (8.97-38.54). Being overweight (BMI = 25-29.9 kg/m2) vs. normal weight was associated with increased discrimination in White women only: 2.10 (1.11-3.96). Conclusions Novel evidence for a race-sex interaction on perceived weight discrimination, with White women more likely to report discrimination at all levels of overweight and obesity was provided. Pychosocial mechanisms responsible for these differences deserve exploration. © 2013 The Obesity Society.