Rhesus hemolytic disease of the newborn is rarely found after the implementation of anti-D immunoglobulin prophylaxis. However, it may lead to cholestasis, elevated liver transaminases, iron overload and late hyporegenerative anemia when it occurs. Etiology of this type of anemia is not defined yet and treatment is controversial. It is typically recognized after two weeks of life which is characterized by low hemoglobin and reticulocyte count. We have reported a case of a neonate with Rh hemolytic disease with late hyporegenerative anemia that was noted at day 18 of life. We treated this anemia by erythropoietin (EPO) 250 U/kg three times per week. Two weeks after initiation of erythropoietin treatment, a stable hemoglobin was noted along with an increased reticulocyte count. The patient required one further blood transfusion in the third week of therapy. Other associated findings were self-limited. A year of follow-up showed an appropriate development for age.