Krüppel-like factors (KLFs) are a family of transcription factors with 3 Cys2/His2 zinc fingers that regulate cell differentiation and developmental processes. EKLF is involved in primitive and definitive erythropoiesis; KLF2 is implicated in the development of primitive erythroid and endothelial cells of the vasculature. Using light and electron microscopy, the yolk sacs and dorsal aortae from EKLF/KLF2 double knockout (KO) E9.5 (embryonic day 9.5) were examined to determine whether these KLFs have compensatory functions in morphology of blood cells and vessels. EKLF/KLF2 double KO E9.5 erythroid, endothelial, and mesothelial cells had more severely abnormal morphology than WT and KLF2-/-. Flow cytometry and cytospins were used to determine maturational effects of single and EKLF/KLF2 double KO primitive erythroid cells double-labeled with anti-TER119 and anti-CD71. EKLF KO and EKLF/KLF2 double KO erythroid cells display defective erythroid maturation. EKLF and KLF2 have overlapping roles in the development of embryonic erythroid and endothelial cells.