Little is known about carotenoids, a diverse group of plant compounds with antioxidant activity, and their association with diabetes, a condition characterized by oxidative stress. Data from phase I of the Third National Health and Nutrition Examination Survey (1988–1991) were used to examine concentrations of α-carotene, β-carotene, cryptoxanthin, lutein/zeaxanthin, and lycopene in 40- to 74-year-old persons with a normal glucose tolerance (n = 1,010), impaired glucose tolerance (n = 277), newly diagnosed diabetes (n = 148), and previously diagnosed diabetes (n = 230) based on World Health Organization criteria. After adjustment for age, sex, race, education, serum cotinine, serum cholesterol, body mass index, physical activity, alcohol consumption, vitamin use, and carotene and energy intake, geometric means of β-carotene were 0.363, 0.316, and 0.290 μmol/liter for persons with a normal glucose tolerance, impaired glucose tolerance, and newly diagnosed diabetes, respectively (p = 0.004 for linear trend), and geometric means for serum lycopene were 0.277, 0.259, and 0.231 μmol/liter, respectively (p = 0.044 for linear trend). All serum carotenoids were inversely related to fasting serum insulin after adjustment for confounders (p < 0.05 for each carotenoid). If confirmed, these data suggest new opportunities for research that include exploring a possible role for carotenoids in the pathogenesis of insulin resistance and diabetes. Am J Epidemiol 1999;149:168–76.