Although anti-Jkb is a well-defined cause of severe acute or delayed hemolytic transfusion reactions, it is rarely associated with severe Hemolytic Disease of the Newborn (HDN), even with high antibody titer. To date, only 13 cases have been reported, so the possible reasons for that still remain unclear. Most of HDN due to anti-Jkb are mild-to-moderate, and usually have a good prognosis. A 41-years-old woman, who had a positive antibody screening test in her 13th week of pregnancy, was sent to the blood bank for study before an amniocentesis. Antibody identification and red blood cell (RBC) phenotyping of the patient and his husband were performed, plus arrays study in the amniotic fluid. An anti-Jkb was identified in the patient's serum with a titer of 1:1, and her RBC phenotype was O Rh(D) positive, C(+), c(+), E(-), e(+), K(-), Jka(+), Jkb(-). The RBC genotype of the fetus was B Rh(D) positive, Jka(+), Jkb(+). Antibody titer remained stable and the pregnancy was uneventful. At birth, there was no need of phototherapy or exchange transfusion for the newborn and her Jk(b+) typing result was confirmed in a cord blood sample. Although most of HDN cases due to anti-Jkb have a good outcome, monitoring antibody titer should be done to prevent fatal complications. Furthermore, antenatal antibody screening should be performed in every pregnant woman irrespective of her Rh(D) antigen status in order to detect red cell alloimmunization to other clinically significant blood group antigens.