We examined the relation of dietary fiber, fat, and other dietary factors to levels of highly sensitive C-reactive protein (CRP) in 4,900 adult participants in the 1999 to 2000 National Health and Nutrition Examination Survey (NHANES 99-00), which was a cross-sectional study of a nationally representative sample of noninstitutionalized United States residents. After controlling for demographic factors, body mass index, smoking, alcohol consumption, exercise, and total caloric intake, subjects in the third and fourth highest quartiles of fiber consumption had a lower risk of elevated CRP (odds ratio [OR] 0.64, 95% confidence interval [CI] 0.43 to 0.96; OR 0.58, 95% CI 0.38 to 0.88, respectively) compared with the lowest quartile. Saturated fat consumption was modestly associated with elevated CRP (third quartile: OR 1.58, 95% CI 1.02 to 2.44; fourth quartile 1.44, 95% CI 0.80 to 2.58). The findings suggest that inflammation may link dietary fiber and fat to cardiovascular disease.