The essential role of transferrin in mammalian iron metabolism is firmly established. Integral to our understanding of transferrin, studies in hpx mice, a model of inherited transferrin deficiency, have demonstrated that transferrin is essential for iron delivery for erythropoiesis and in the regulation of expression of hepcidin, a hormone that inhibits macrophage and enterocyte iron efflux. Here we investigate a potential role for transferrin in the distribution of three other physiologic metals, manganese, copper and zinc. We first assessed metal content in transferrin-rich fractions of wild-type mouse sera and demonstrate that while both iron and manganese cofractionate predominantly with transferrin, the absolute levels of manganese are several orders of magnitude lower than those of iron. We next measured metal content in multiple tissues in wild-type and hpx mice at various ages. Tissue metal imbalances were severe for iron and minimal to moderate for some metals in some tissues in hpx mice. Measurement of metal levels in a transferrin-replete yet hepcidin-deficient and iron-loaded mouse strain suggested that the observed imbalances in tissue copper, zinc and manganese levels were not all specific to hpx mice or caused directly by transferrin deficiency. Overall, our results suggest that transferrin does not have a primary role in the distribution of manganese, copper or zinc to tissues and that that the abnormalities observed in tissue manganese levels are not attributable to a direct role for transferrin in manganese metabolism but rather to an indirect effect of transferrin deficiency on hepcidin expression and/or iron metabolism.