There is a paucity of data on the prevalence of the Rhesus (Rh) induced erythrocyte alloimmunization other than the notorious Rh-D antigen among the Indians. This is evident more so mainly due to the sub-optimal antenatal care provided to the women here. We describe herein, a case of hemolytic disease of the newborn due to anti-Rh (E) specificity in a newborn of an O Rh (D) positive first-time mother, who hailed from a rural background in India. The baby’s rising bilirubin levels [> 20 mg/dL] warranted an urgent double volume exchange transfusion. Gradually the baby’s clinical condition improved and was discharged from the hospital on the 19th day of his birth. Currently, the baby is doing well with optimal developmental milestones.