We examined the relationships between selected perinatal and early infancy factors (maternal smoking during pregnancy, infant low birthweight, breastfeeding, and early introduction of solid foods [<6 months of age] and increased BMI [≥85th, ≥95th percentiles for age, sex]), waist circumference (WC), C-reactive protein (CRP), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, and decreased HDL cholesterol during early childhood. The population-based sample included 3,644 3-to-6-year-old Non-Hispanic White (NHW), Hispanic, and Non-Hispanic Black (NHB) children who participated in the 1999-2008 National Health and Nutrition Examination Surveys. Analysis showed that breastfeeding was significantly protective against early childhood obesity (OR 0.43, 95% CI, 0.27-0.69) and the highest quintile for WC (OR 0.58, 95% CI, 0.37-0.32) among NHW, and against the highest quintile of non-HDL cholesterol among NHB (OR 0.56, 95% CI, 0.32-0.98). Additionally, NHW children were significantly more likely to be obese (OR 2.22, 95% CI 1.30-3.78) and have higher CRP levels (OR 1.63, 95% CI, 1.05-2.51) if their mothers smoked during pregnancy. These results support the observation that breastfeeding may be protective against early childhood obesity while maternal smoking during pregnancy is a risk factor for obesity and increased CRP levels among NHW young children.