OBJECTIVE - Insulin resistance and C-reactive protein (CRP) levels are strongly correlated in adults. This study explored the relationship in youth. RESEARCH DESIGN AND METHODS - Associations between CRP levels, cardiovascular risk, and insulin resistance measured by the euglycemic clamp were investigated in 342 healthy Minneapolis youth. RESULTS - There was no difference in mean CRP levels among boys (n = 189, CRP 1.10 ± 0.46 mg/l) and girls (n = 153, CRP 1.16 ± 0.63 mg/l; P = 0.32). There was also no difference between CRP and Tanner stage. CRP, adjusted for BMI, was significantly greater in black subjects compared with white subjects (P = 0.03). CRP was strongly related to adiposity in both girls and boys. CRP levels were related to fasting insulin levels (r = 0.16, P = 0.003) but this association was not significant after adjustment for BMI (r = 0.07, P = 0.21). Similarly, M, the euglycemic clamp measurement of insulin sensitivity, was significantly related to CRP levels (r = -0.13, P = 0.02) but not when M was normalized to lean body mass (M 1bm) (r = -0.10, P = 0.09). There was a significant inverse correlation between M1bm and CRP quartiles, which disappeared after adjustment for BMI. There was no significant association between CRP levels and lipids, blood pressure, physical activity, or left ventricular mass. CONCLUSION - In contrast to adult subjects, after adjustment for adiposity, CRP levels in children age 10-16 years were not significantly associated with insulin resistance or with other factors comprising the metabolic syndrome. This is consistent with the concept that insulin resistance may precede the development of CRP elevation in the evolution of the metabolic syndrome.