OBJECTIVE: To explore relationships between C-reactive protein (CRP), subclinical infection, insulin resistance, and metabolic syndrome. RESEARCH DESIGN AND METHODS: Data from 1,174 Eskimos, aged >/=18 years, from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study were analyzed; 40 participants with diabetes were eliminated. Baseline assessment included interviews, physical exam, and blood and urine sampling. Metabolic syndrome was assessed using Adult Treatment Panel III criteria. CRP and antibodies to common pathogens were measured. RESULTS: Although CRP was related in univariate analyses to insulin resistance and metabolic syndrome, relations were attenuated or eliminated after adjustment for relevant covariates. CRP was not higher among those with impaired fasting glucose (IFG), and pathogen burden was not related to insulin resistance, metabolic syndrome, or IFG. CONCLUSIONS: Pathogen burden and inflammation do not seem to be related to insulin resistance, metabolic syndrome, or IFG in this population. The inflammatory process may reflect insulin resistance or its correlates but most likely is not causative.