Objective. Human adipose tissue expresses and releases the proinflammatory cytokine interleukin-6, potentially inducing low-grade systemic inflammation in persons with excess body fat. To limit potential confounding by inflammation-related diseases and subclinical cardiovascular disease, we tested the hypothesis that overweight is associated with low-grade systemic inflammation in children. Design and Setting. The third National Health and Nutrition Examination Survey, 1988–1994, a representative sample of the US population. Participants. A total of 3512 children 8 to 16 years of age. Outcome Measures. Elevated serum C-reactive protein concentration (CRP; ≥.22 mg/dL) and white blood cell count (109 cells/L). Results. Elevated CRP was present in 7.1% of the boys and 6.1% of the girls. Overweight children (defined as having a body mass index or a sum of 3 skinfolds (triceps, subscapula, and supra-iliac) above the gender-specific 85th percentile) were more likely to have elevated CRP than were their normal-weight counterparts. After adjustment for potential confounders, including smoking and health status, the odds ratio (OR) was 3.74 (95% confidence interval [CI]: 1.66–8.43) for overweight boys and the OR was 3.17 (95% CI: 1.60–6.28) for overweight girls, based on the body mass index. Based on the sum of 3 skinfolds, these ORs were 5.11 (95% CI: 2.36–11.06) and 2.89 (95% CI: 1.49–5.59) for boys and girls, respectively. Overweight was also associated with statistically significant higher white blood cell counts. The results were similar when restricted to healthy, nonsmoking, nonestrogen-using children. Conclusions. In children 8 to 16 years of age, overweight is associated with higher CRP concentrations and higher white blood cell counts. These findings suggest a state of low-grade systemic inflammation in overweight children. inflammation, obesity, children.