We examined the relationship of elevated depressive symptoms with antioxidant status. Cross-sectional data from the National Health and Nutrition Examination Surveys 2005–6 on US adults aged 20–85 years were analysed. Depressive symptoms were measured using the Patient Health Questionnaire with a score cut-off point of 10 to define ‘elevated depressive symptoms’. Serum antioxidant status was measured by serum levels of carotenoids, retinol (free and retinyl esters), vitamin C and vitamin E. The main analyses consisted of multiple logistic and zero-inflated Poisson regression models, taking into account sampling design complexity. The final sample consisted of 1798 US adults with complete data. A higher total serum carotenoid level was associated with a lower likelihood of elevated depressive symptoms with a reduction in the odds by 37 % overall with each sd increase in exposure, and by 34 % among women (P< 0·05). A dose–response relationship was observed when total serum carotenoids were expressed as quartiles (Q4 (1·62–10·1 μmol/l)v. Q1(0·06–0·86 μmol/l): OR 0·41; 95 % CI 0·23, 0·76, P< 0·001; P for trend = 0·035), though no significant associations were found with the other antioxidant levels. Among carotenoids, β-carotene (men and women combined) and lutein+zeaxanthins (women only, after control for dietary lutein+zeaxanthin intake and supplement use) had an independent inverse association with elevated depressive symptoms among US adults. None of the other serum antioxidants had a significant association with depressive symptoms, independently of total carotenoids and other covariates. In conclusion, total carotenoids (mainly β-carotene and lutein+zeaxanthins) in serum were associated with reduced levels of depressive symptoms among community-dwelling US adults.