Cross-sectional interactions by malaria status were investigated between plasma alpha-tocopherol, retinol, and several carotenoids (lutein, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene) and indicators of disease severity (blood parasite count, hemoglobin concentration), acute-phase response (plasma albumin and ceruloplasmin concentrations), hepatic involvement (plasma alanine aminotransferase), oxidant status and antioxidant status (plasma thiobarbituric acid-reactive material and ascorbate), nutritional (weight-for-age) and carrier protein [retinol binding protein (RBP)] status, and cholesterol concentration (as a proxy for lipoprotein) in 100 consecutively admitted children with malaria. There were 50 children with severe and 50 with mild malaria and 50 age- and sex-matched control subjects. alpha-Tocopherol, retinol, and all the carotenoid concentrations were lower in the patients than in the control subjects (P < 0.001). The differences were greater in severe than in mild malaria, except for lutein. in severe malaria only, both retinol and alpha-tocopherol correlated with albumin, ceruloplasmin, and REP concentrations whereas in all three groups retinol correlated with REP and alpha-tocopherol correlated with cholesterol (all P < 0.01)). Using multivariate analysis on data from all patients combined, cholesterol was the most significant factor explaining the variance in alpha-tocopherol (29%) whereas REP was responsible for 95% of the variance in retinol. Plasma cholesterol and REP values in rum (in the absence of alpha-tocopherol and retinol, respectively) were influenced primarily by acute-phase markers (mainly albumin and ceruloplasmin). Alanine aminotransferase (r = -0.17) and thiobarbituric acid-reactive material (r = -0.17) also showed a small contribution to the variance of REP but 60-70% remained unexplained. In conclusion, low plasma lipid-soluble micronutrient concentrations in malaria are strongly influenced by the reductions in their carrier molecules, which, in turn, are low as a consequence of the acute-phase response.