Background: The term kernicterus refers to the clinical features of bilirubin encephalopathy. Its risk is increased in term babies with very high bilirubin levels. Kernicterus is also known to occur at lower levels of bilirubin in term babies who have risk factors and in preterm babies. Objective: The aim of the present study was to investigate whether serum alkaline phosphatse & haptoglobin (Hp) level could be used for the early diagnosis and prediction of hyperbilirubinemia in newborns. Methodology: The study is a prospective clinical study design, which was carried out in Pediatric Department, Faculty of Medicine, Aswan University Hospital. The study included 100 newborns with gestational age more than 35wk delivered in obstetric department. Results: Our study showed no statistically significant difference between jaundiced and non- jaundiced cases regarding the mode of delivery, maternal gravidity and parity. As regards previous sibiling affected, we found a significant relation between clinically appearing jaundice and previous sibling affected with neonatal hyperbillirubinemia, which may reflect genetic susceptibility for hyperbillirubinemia. No significant relationship between gestational age and clinically appearing jaundice. When assessing the relationship between clinically appearing jaundice and birth weight, our results revealed no significant relationship. Conclusion: The cord blood alkaline phosphatase level is not only a useful predictor for severe neonatal jaundice but also can predict the early onset of neonatal hyperbilirubinemia and expected methods of treatment in healthy newborns more than 35 weeks gestational age.