BACKGROUND: Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) are man-made compounds with widespread presence in human sera. In previous occupational and adult studies, PFOA and PFOS were positively associated with serum lipid levels. OBJECTIVE: To interrogate associations between PFOA and PFOS and serum lipids in children and adolescents. DESIGN: Cross-sectional community-based study. SETTING: Mid-Ohio River Valley. PARTICIPANTS: A total of 12 476 children and adolescents included in the C8 Health Project, which resulted from the pretrial settlement of a class action lawsuit pursuant to PFOA contamination of the drinking water supply. MAIN OUTCOME MEASURES: Serum lipids (total, high-density lipoprotein [HDL-C], and low-density lipoprotein [LDL-C] cholesterol and fasting triglycerides). RESULTS: Mean (SD) serum PFOA and PFOS concentrations were 69.2 (111.9) ng/mL and 22.7 (12.6) ng/mL, respectively. In linear regression after adjustment for covariables, PFOA was significantly associated with increased total cholesterol and LDL-C, and PFOS was significantly associated with increased total cholesterol, HDL-C, and LDL-C. Using general linear model analysis of covariance, between the first and fifth quintiles of PFOA there was a 4.6-mg/dL and a 3.8-mg/dL increase in the adjusted mean levels of total cholesterol and LDL-C levels, respectively, and an 8.5-mg/dL and a 5.8-mg/dL increase in the adjusted mean levels of total cholesterol and LDL-C, respectively, between the first and fifth quintiles of PFOS. Increases were 10 mg/dL for some age- and sex-group strata. Observed effects were nonlinear, with larger increases in total cholesterol and LDL-C levels occurring at the lowest range, particularly of PFOA. CONCLUSION: Although the epidemiologic and cross-sectional natures of this study limit causal inferences, the consistently observed associations between increasing PFOA and PFOS and elevated total cholesterol and LDL-C levels warrant further study.