Diets high in fruits and vegetables are generally believed protective against several chronic diseases. One suggested mechanism is a reduction in oxidative stress. The carotenoids, nutrients found in colored fruits and vegetables, possess antioxidant properties in vitro, but their role in humans is less well documented. The aim of this cross-sectional study was to explore the relationships between the most abundant plasma carotenoids (alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin and beta-cryptoxanthin), as well as grouped carotenoids (total xanthophylls, carotenes and carotenoids), and urinary excretion of the F(2)-isoprostanes (F(2)-IsoPs), stable and specific biomarkers of oxidative damage to lipids. Two F(2)-IsoP measures were utilized: total F(2)-IsoPs and 8-iso-PGF(2alpha). The study population (N = 52) was drawn from a study among patients curatively treated for early-stage head and neck cancer. Unadjusted linear regression analyses revealed significant inverse associations between plasma lutein, total xanthophylls and both F(2)-IsoP measures at baseline. After control for potential confounders, all individual and grouped xanthophylls remained inversely associated with the F(2)-IsoP measures, but none of these associations achieved significance. The carotenes were not inversely associated with total F(2)-IsoPs or 8-iso-PGF(2a) concentrations. The finding of consistent inverse associations between individual and grouped xanthophylls, but not individual and grouped carotenes, and F(2)-IsoPs is intriguing and warrants further investigation.