ABCme is an ATP Binding Cassette transporter expressed in the inner membrane of the mitochondria. It is highly expressed in heme producing tissues and has been found to enhance hemoglobin production. However, its physiological role in vivo as well its biochemical function had not been elucidated. Based on the existing evidence we hypothesized that ABCme could be critical for hematopoiesis and involved in managing mitochondrial oxidative stress. To test this hypothesis we characterized the newly generated ABCme-/- mouse, looking specifically at erythroid development. We determined the ABCme-/- mice are embryonic lethal and display impaired blood development. We found increased cell death in proerythroblast erythroid progenitors from the ABCme-/- embryo. Erythroid cells from the ABCme-/- also displayed elevated mitochondrial oxidative damage, and in vitro treatment with antioxidants was capable of rescuing cell death and hemoglobin production in ABCme-/- cells. Furthermore, adult ABCme+/- mouse display phenotypic aplastic anemia characterized by dysmyelopoiesis. Additionally, the aged ABCme+/- mice developed NAFLD and displayed altered drug metabolism related to CYP450 activity. Our findings indicate that ABCme is involved in management of oxidative stress associated with the heme biosynthetic pathway. It also suggests that ABCme may participate in multiple pathologic conditions surrounding heme biosynthesis and mitochondrial oxidative stress.