The aim of this article is to longitudinally investigate racial differences in serum adiponectin and leptin in European-American (EA) and African-American (AA) women in the overweight and weight-reduced states. Sixty-two EA and 58 AA premenopausal women were weight reduced from body mass index (BMI) 27-30 kg/m(2) to BMI ≤ 24. Fasting serum adiponectin and leptin were determined; body composition and intra-abdominal adipose tissue (IAAT) were measured with dual-energy X-ray absorptiometry and computed tomography, respectively. In repeated-measure MANOVA, there was a significant race effect for IAAT and total fat mass; compared to AA women, EA women had higher IAAT and total fat mass (p < 0.0001 and p = 0.027, respectively). In the mixed-model for adiponectin that adjusted for IAAT, limb fat, and total fat, race was significantly associated with adiponectin (p = 0.046). AA women had significantly lower adjusted adiponectin compared to EA women at baseline [7.67 (6.85, 8.60) vs. 9.32 (8.34, 10.4) μg/ml, p < 0.05] and following weight loss [9.75 (8.70, 10.9) vs. 11.8 (10.6, 13.2) μg/ml, p < 0.05]. In a mixed-model for leptin that adjusted for insulin, estradiol, and fat mass, race was significantly associated with leptin (p < 0.0001). AA women had significantly higher adjusted leptin compared to EA women at baseline [24.7 (22.3, 27.4) vs. 19.9 (18.1, 21.8) ng/dl, p < 0.05] and following weight loss [11.7 (10.2, 13.3) vs. 8.48 (7.50, 9.57) ng/dl, p < 0.05]. Despite having a more favorable body fat distribution, AA women had lower adjusted adiponectin and higher leptin. Differences in body composition and fat distribution do not appear to be significant factors in explaining lower adiponectin and higher leptin in AA women.