The objective of this study was to test the hypothesis that the effect of a high-fat meal (HFm) on plasma lipid-soluble antioxidants and biomarkers of vascular oxidative stress and inflammation would be attenuated by short-term lycopene supplementation in young healthy subjects. Following restriction of lycopene-containing foods for 1-wk (LYr), blood was collected in a fasting state and 3 h after a HFm and a low-fat meal (LFm) in N = 18 men aged 23 +/- 2 years, and after a HFm only in N = 9 women aged 23 +/- 1 years. Blood was also sampled pre- and post-meals following 1-wk of 80 mg/day lycopene supplementation (LYs) under continued dietary LYr. In the fasting state, LYs compared with LYr not only evoked a >2-fold increase in plasma lycopene but also increased plasma beta-carotene and alpha-tocopherol (p < 0.01), though LYs did not affect plasma nitrate/nitrite (biomarker of nitric oxide), malondialdehyde (biomarker of lipid oxidative stress), vascular- and intercellular-adhesion molecules or C-reactive protein (biomarkers of inflammation). Contrary to the hypothesis, the HFm-induced dyslipidemic state did not affect plasma malondialdehyde, C-reactive protein, or adhesion molecules in either LYr or LYs. Both the HFm and LFm were associated with decreases in the nitric oxide metabolites nitrate/nitrite and lipid-soluble antioxidants (p < 0.05). The data revealed that 1-wk of LYs increased plasma lycopene, beta-carotene, and alpha-tocopherol yet despite these marked changes to the plasma lipid-soluble antioxidant pool, biomarkers of vascular oxidative stress and inflammation were unaffected in the fasted state as well as during dyslipidemia induced by a HFm in young healthy subjects.