To examine associations between serum antioxidant levels and mortality (all-cause, cancer and CVD) among US adults. We examined the risk of death from all-cause and cause-specific mortality associated with serum antioxidant (vitamin E and carotenoids) and vitamin A levels using Cox regression models to estimate hazards ratios (HR) and 95 % CI. The National Health and Nutrition Examination Survey (NHANES) 1999-2002 was followed up through 31 December 2015. The NHANES 1999-2002 cohort included 8758 participants aged ≥ 20 years. Serum carotenoid levels were only assessed for the 1999-2000 cycle. Therefore, sample size for each assessed antioxidant ranged from 4633 to 8758. Serum vitamin E level was positively associated with all-cause mortality (HR = 1·22, 95 % CI 1·04, 1·43, highest v. lowest quartile). No other antioxidants were associated with mortality in overall analysis. In race/ethnicity-specific analyses, high vitamin E and α-tocopherol levels were associated with increased risk of all-cause mortality among non-Hispanic Whites. Among non-Hispanic Blacks, serum α-tocopherol level was associated with decreased risk of cancer mortality (HR = 0·30, 95 % CI 0·12, 0·75, third v. first quartile) and total carotenoid levels with reduced risk of CVD mortality (HR = 0·26; 95 % CI 0·07, 0·97, second v. lowest quartile). Hispanics with high β-carotene levels had reduced risk of CVD mortality. Serum antioxidant levels may be related to mortality; these associations may differ by race/ethnicity and appeared to be non-linear for all-cause and cause-specific mortality. Further studies are needed to confirm our results.