Although most newborns develop some degree of jaundice, bilirubin levels high enough to put a newborn at risk of bilirubin encephalopathy and kernicterus are rare but still occur in Egypt. The aim of current study was to assess the magnitude of neonatal jaundice and detect possible etiologies. This study included retrospective analysis of the data of all jaundiced cases admitted to NICU of Cairo University Pediatric Hospital during the period from the first January to the end of December 2007 and the data of the referred neonatal cholestatic cases in hepatology unit at the same hospital. In the study period, there were 808 patients having neonatal jaundice who were admitted to neonatal intensive care unit with a mean age of 5.74±4 days and a mean weight of 2658.6±710 grams. They represented 72.9% of all cases admitted in the year 2007. Neonatal jaundice alone as a cause of admission represented 54.1% of all cases admitted. The mean total bilirubin level at day of presentation was 23.1±9.87 mg/dl. It was found that ABO incompatibility, Rh incompatibility and sepsis (18.7%, 5.8% and 12.5% respectively) are the main causes of indirect hyperbilirubinaemia. In 56% of cases the cause was unknown. It was found that 325 (40%) studied cases had extreme hyperbilirubinemia with peak of total bilirubin ≥25 mg/dl. Phototherapy was the only therapy in 68.4% of cases while 29.9% required exchange transfusion. Eleven (1.4%) cases were discharged with frank kernicterus. Among 23 referred cholestatic cases, it was found that inspissated bile syndrome then neonatal sepsis and extrahepatic biliary atresia are the main causes of neonatal cholestasis. From this study, we concluded that, neonatal jaundice is still a major problem in our community. The main causes are ABO incompatibility, Rh incompatibility and sepsis especially in extreme hyperbilirubinemia which shows high prevalent in the NICU population. Any infant with direct hyperbilirubinemia should be diagnosed to rule out cholestatic liver disease.