Abstract Background: Jaundice is a clinical condition that is often present in pediatric practice and constitutes one of the major issues within the neonatal period and it is either physiological or pathological. Although most newborn who have jaundice are otherwise healthy, they need close monitoring for serum bilirubin level as bilirubin is potentially toxic to the central nervous system. Risk factors may be maternal or neonatal in origin. This preliminary study focuses on the detection of the risk factors of pathological unconjugated hyperbilirubinemia due to lack of information on this topic in Yemen. Aim of Study: To determine the most common aetiology and risk factors of pathological unconjugated hyperbilirubine-mia and their relation to serum bilirubin. Patients and Methods: The study was prospective cross-sectional descriptive study of newborns with pathological unconjugated hyperbilirubinemia admitted to neonatal intensive care unit (NICU) at Al-Thawra General Modern Teaching Hospital and Al-Sabeen Maternity and Childhood Teaching Hospital during a period of 12 months starting on June 2012 to end of May 2013.Of the total admitted cases, two hundred cases were selected according to the inclusion and exclusion criteria. Data was collected, tabulated and analyzed by using Statistical Package for the Social Sciences (SPSS) version 20. Results: The risk factors of pathological hyperbilirubine-mia were Neonatal sepsis which was the most common aeti-ology and associated risk factor and was present in 70% of the cases, ABO incompatibility was present in 14% of the cases, Rh incompatibility was present in 8% of the cases, Cephalohaematoma (excessive bruising) was present in 6% of the cases, and G6PD deficiency was present in 2% of the cases. Conclusion: Pathological unconjugated hyperbilirubinemia is one of the major problems in neonatal morbidity and mortality in Yemen. Neonatal sepsis was the commonest aetiology and associated risk factor of pathological hyperbi-lirubinemia and the major cause of death in this study. We need to do early screening for detecting hyperbilirubinemia and we need to adopt early essential newborn care and resus-citation guideline on a national level to conduct appropriate management.