Hemolytic disease of the fetus and newborn is a syndrome associated with immune destruction of the fetal and newborn red cells by maternal red cell alloantibodies. The detection of anti-M in antenatal screening can be responsible for neonatal red cell aplasia. A 32-h-old full-term neonate admitted with inconsolable cry and mild fever. Laboratory tests revealed progressive anemia and hyperbilirubinemia on day 3. The peripheral blood smear showed evidence of hemolysis and reticulocyte count was reduced. Intensive phototherapy and antibiotics were started after ruling out other causes of hyperbilirubinemia. Blood group typing and advanced red cell serology workup were done. Antibody screening and identification was suggestive of the presence of anti-M antibody in both mother and baby. Intravenous immunoglobulin and red blood cell transfusions were given. Anti-M is capable of causing hemolytic disease of the fetus and newborn and prolonged anemia. Newborns with anemia should be evaluated for all the possible causes to establish a diagnosis.