Maternal obesity may be associated with metabolic factors that affect the intrauterine environment, fetal growth, and the offspring's long-term risk for chronic disease. Among these factors, maternal serum lipids play a particularly important role. Our objective was to estimate the influence of variation in maternal serum lipid levels on variation in infant birth weight (BW) in overweight/obese and normal weight women. In a prospective cohort of 143 gravidas, we measured maternal serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) at 6-10, 10-14, 16-20, 22-26, and 32-36 weeks gestation. Effects of maternal serum lipid levels on infant BW adjusted for gestational age at delivery (aBW) were analyzed using linear regression models. In analyses stratified by maternal prepregnancy BMI categorized as normal (25.0kg/m2) and overweight/obese (25.0kg/m 2), we found a significant (P<0.05) inverse association between aBW and HDL-C at all time points starting at 10 weeks gestation in overweight/obese women. No significant effect was found in normal weight women. In contrast, increased maternal serum TG was significantly associated with increased aBW only for normal weight women at 10-14 and 22-26 weeks gestation. Variation in aBW is not associated with variation in maternal serum TC or LDL-C for either stratum at any time point. We postulate that such differences may be involved in the physiological programming that influences later risk of chronic disease in the infants of overweight/obese mothers.