Se, a micronutrient essential for human health, is incorporated into at least 25 selenoproteins including selenoprotein P (SePP), which transports Se within the body. This research identified two SNPs in the SePP gene, one in the coding region (position 24731, causing an Ala to Thr change) and one in the 3 &prime untranslated region (position 25191). Their frequency was similar in Caucasian, Chinese and South Asian populations. Prospectively-genotyped volunteers were supplemented for 6 weeks with 100 &mu g sodium selenite / day. Blood samples were analysed for plasma Se and selenoprotein biomarkers at baseline, after supplementation and during a wash-out period. Plasma Se, SePP and glutathione peroxidase 3 (GPx3) levels increased with supplementation. Baseline plasma Se content depended on both SePP genotypes and body mass index. Pre-supplementation SePP concentration was associated with gender and genotype at SNP 24731 and post-supplementation concentration with SNP 25191. Both SNPs and gender were associated with differences in GPx3 activity, plasma and erythrocyte thioredoxin reductase 1 concentrations and lymphocyte glutathione peroxidase 1 and 4 activities and concentrations. In conclusion, the data reveal two common functional SNPs within the human SePP gene which may predict behaviour of biomarkers of Se status and response to supplementation and thus susceptibility to disease.