Turkeys and chickens reared to 5-weeks of age and fed diets with feedstuffs low in endogenous tocopherols were examined. Treatments included feed supplemented with RRR (natural source vitamin E) alpha tocopheryl acetate (AcT, 35 mg/kg feed) and all-racemic (synthetic vitamin E) AcT (10 and 58 mg/kg feed). AcT ingestion per kg body weight was statistically similar between chicken and turkey only when the RRR-AcT containing diet was fed. Metabolites of alpha tocopherol (AT) and gamma tocopherol (GT) were measured in bile. When fed the RRR AcT diet, AT- and GT-metabolites were 8.3 and 5.3-fold elevated in turkey compared to chicken, respectively (p<
0.001). When fed all-racemic AcT at 58 mg/kg feed, AT- and GT-metabolites were 2.2 and 2.4-fold elevated in turkey compared to chicken, respectively (p<
0.01) with AcT ingestion per kg body weight 1.29-fold higher in the chickens (p<
0.001). Turkey cytochrome P450 2C29 (CYP2C29) was increased relative to its chicken ortholog based on both RNA-Seq (p<
0.001) and activity-based protein profiling (p<
0.01) of liver tissue. Turkey CYP3A9 and CYP4F22 were increased compared to their chicken orthologs using as determined by Activity- Based Protein Profiling (p<
0.05). The 3A and 4F family are noted as tocopherol hydroxylases in mammals. Alpha tocopherol concentrations in plasma, liver and muscle from turkey were 1.7 to 4.7-fold lower than the respective tissues from chicken (p<
0.05). Lipid oxidation occurred more rapidly in turkey thigh compared to chicken thigh (p<
0.05). These studies suggest that elevated tocopherol metabolism by cytochrome P450 hydroxylases in turkey liver contribute to the decreased accumulation of tocopherols in turkey tissues compared to that of chicken.