AIMS: The aim of this study was to investigate the relationship between maternal anti-A\-B titers and the values of hemoglobin and indirect bilirubin in ABO-hemolytic disease of the newborn (ABO-HDN) afflicted newborns and to develop a cutoff of total and immunoglobulin G (IgG) antibodies for treatment needs in neonates in Latakia. STUDY DESIGN: A case–control study of 40 positive direct antiglobulin test (DAT) neonates who were ABO incompatible with their mothers and 20 healthy DAT-negative ABO incompatible neonates. Total and IgG anti-A\-B titers were compared between the two groups, and their correlation with newborns' hemoglobin and indirect bilirubin and the need for treatment were evaluated. RESULTS: Both the maternal anti-A\-B total and IgG titers in the ABO-HDN group were significantly higher than in the control group (P < 0001). A significant correlation between maternal IgG titers and indirect bilirubin was found, but not between total antibody titers and indirect bilirubin. A negative correlation between total and IgG titers and hemoglobin was also documented. The IgG cutoff value for ABO-HDN incidence and the need for treatment was 128 with sensitivity and specificity of 92.5% and 95%, and the total antibodies cutoff value was 64, with a sensitivity and specificity of 62.5% and 90%, respectively. CONCLUSION: Maternal total and IgG anti-A\-B can be an important prediction for the occurrence of ABO-HDN and evaluation of the neonates' hyperbilirubinemia after birth. Therefore, the routine detection of the titer of these antibodies and especially in mothers who have a high antibodies titer and a record of a previous jaundiced neonate can be an additional step in the ABO-HDN assessment of neonate.