HIF1 and HIF2 are major mediators for hypoxia sensing and response. Their roles in early differentiation of two key cell types involved in oxygen supply in amniotes, the primitive blood cells and endothelial cells, are unclear. We show that, in pre-circulation avian embryos, hif1alpha and hif2alpha are expressed in embryonic and extraembryonic tissues, respectively. hif2alpha, first identified as epas1, is not present in endothelial cells at any pre-circulation stage under either normoxia or hypoxia conditions. Differentiating blood cells express low levels of hif2alpha under normoxia, but show a strong and rapid upregulation under hypoxia. Blood cell differentiation, however, is not affected under either hypoxia or hyperoxia conditions.