BACKGROUND: Blood vitamin E concentrations are modulated by dietary, metabolic, and genetic factors. CD36 (cluster of differentiation 36), a class B scavenger receptor, might be involved in tissue vitamin E uptake and thus would influence blood vitamin E concentrations. OBJECTIVE: The goal of the study was to assess the association between CD36 single nucleotide polymorphisms (SNPs) and plasma α-tocopherol concentrations in humans. DESIGN: A subsample from the adult SU.VI.MAX (SUpplementation en VItamines et Minéraux AntioXydants) cohort (n = 621) and the adolescent cross-sectional HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study (n = 993) were genotyped for CD36 SNPs (4 and 10 SNPs, respectively). Fasting plasma α-tocopherol concentrations were assayed by using HPLC. Associations were determined by haplotype analyses and by general linear regression models. RESULTS: In the SU.VI.MAX subsample, haplotype analyses showed that some haplotypes of SNPs rs1984112, rs1527479, rs7755, and rs1527483 tended to be associated with plasma α-tocopherol concentrations (P = 0.08 and P = 0.09 for haplotypes 1222 and 1122, respectively). We then investigated the whole known common genetic variability (10 SNPs) of CD36 in the HELENA Study. Three SNPs were associated with lower plasma α-tocopherol concentrations (rs1984112: -3.2%, P = 0.053; rs1761667: -2.9%, P = 0.046; rs1527479: -3.7%, P = 0.0061). After correction for multiple testing, the association between rs1527479 and α-tocopherol concentrations remained significant. This association was modulated by concentrations of fasting serum triglycerides (P for interaction = 0.006) and long-chain polyunsaturated fatty acids (P for interaction = 0.005). CONCLUSION: Our results suggest that CD36 can modulate blood α-tocopherol concentrations and may therefore be involved in the intestinal absorption or tissue uptake of vitamin E.