Using data from the National Health and Nutrition Examination Survey (NHANES, 1999-2002), we examined the association of secondhand tobacco exposure, estimated by serum cotinine, with serum C-reactive protein (CRP) concentrations in nonsmoking participants, aged 6-18 years. The association between serum cotinine and serum CRP was analyzed using multiple linear regression, with adjustment for other study variables. All analyses used weighted data and adjustments for design effects. Multiple regression analysis indicated that a change in serum cotinine of 0.5 ng/ml was associated with a 0.96 mg/dl change in CRP (95% CI = 0.93-1.00), even after adjustment for age, white blood cell count, and body mass index percentile. We found a significant association between secondhand smoke exposure, assessed by serum cotinine, and elevated serum CRP among nonsmoking youth. Secondhand smoke exposure may pose an important long-term cardiovascular risk for children and adolescents.