We examined the association between plasma antioxidant levels and markers of inflammation, including C-reactive protein (CRP) and fibrinogen (FG) in US adults. National Health and Nutrition Examination Survey participants examined between 2001 and 2002 were included, if data on CRP or FG levels. Serum vitamins A and E, two retinyl esters, and six carotenoids were measured using HPLC with photodiode array detection. Multivariable-adjusted linear regression analyses accounted for the survey design and sample weights. A total of 784 eligible participants were included; 47·5 % (n 372) were men. In multivariable linear regression models, serum α-carotene, trans-β-carotene, cis-β-carotene, β-cryptoxanthin, combined lutein/zeaxanthin, trans-lycopene, retinyl palmitate, α-tocopherol, retinol and 25-hydroxy vitamin D were negatively associated with serum CRP (P<0·001 for all comparisons). Serum α-carotene, trans-β-carotene, cis-β-carotene, combined lutein/zeaxanthin, trans-lycopene, α-tocopherol, retinol and 25-hydroxy vitamin D were negatively associated with serum FG levels (P<0·001 for all comparisons). In the same model, the risk of CVD, defined as CRP levels >3 mg/l, decreased with increasing levels of antioxidants (α-carotene, trans-β-carotene, cis-β-carotene, vitamins A and E). Furthermore, we found a moderate impact of adiposity on the link between antioxidants and CRP. Our results suggest that the lower the antioxidants levels, the higher the inflammatory burden, based on CRP and FG levels. Adiposity moderately affects this association. Furthermore, an inverse relationship between CVD risk and antioxidant levels was observed. This finding suggests that reduced levels of vitamins with antioxidant properties may predispose to increased CVD risk.