Cats are unique in that they normally have low numbers of Howell-Jolly bodies and Heinz bodies within their erythrocytes. This likely results from poor “pitting” function by the spleen, although increased susceptibility of cat hemoglobin to oxidant damage may also contribute to the presence of Heinz bodies. Reticulocytes in cats are slow to degrade ribosomal material as they mature into erythrocytes, resulting in frequent punctate reticulocytes in normal cat blood. As with all mammals, mature erythrocytes of cats are enucleated and lack mitochondria and ribosomes. They depend on anaerobic glycolysis to generate ATP for metabolic requirements, and cats with hereditary erythrocyte pyruvate kinase deficiency, a rate-limiting enzyme in glycolysis, have hemolytic anemias. The pentose phosphate pathway generates NADPH that is essential in protecting erythrocytes against oxidants, and cat erythrocytes increase pentose phosphate metabolism in response to the oxidant methylene blue at rates similar to human erythrocytes. Anaerobic glycolysis also generates NADH for the reduction of methemoglobin that forms at low rates in mammals, and cats with hereditary erythrocyte cytochrome-b5 reductase deficiency have prominent methemoglobinemia. In contrast to most mammals, cats (as well as most dogs) lack the membrane associated Na+/K+-ATPase pump, resulting in high Na+ and low K+ erythrocytes. Cats (and ruminants) also differ from most mammals by having low affinity hemoglobins and low erythrocyte 2,3-diphosphoglycerate concentrations. Incompatibilities in the AB blood group and the Mik blood group of cats have been recognized to cause transfusion reactions and neonatal isoerythrolysis. The lifespan of cat erythrocytes is about 80 days, which is expected based on their metabolic rates.