Abstract Background: Phototherapy has been the standard of care for the treatment of hyperbilirubinemia in neonates. It is generally safe procedure, although behavioral and neurological side-effects can occur. Aim of Study: To assess behavioral and neurological responses of neonates with jaundice undergoing phototherapy. Subjects and Methods: A descriptive exploratory research design was utilized on a convenient sample of sixty neonates with jaundice, total serum bilirubin level ranged from seven to twenty mg/dl and undergoing phototherapy at the NICU of El-Monera Pediatric Hospital, Cairo University. A neonatal characteristics assessment sheet, and Neonatal Behavioral Assessment Scale (NBAS) were used to collect data from September 2018 to February 2019. After written consent from parents, neonatal characteristics were recorded from the medical sheet and every neonate was assessed individually using (NBAS) two times, before starting and after stopping phototherapy. Results: The current study revealed that all neonates were full term and their mean weight was 2.86±0.53. Behavioral and neurological responses of neonates with jaundice were differed significantly after than before starting phototherapy on the NBAS. Conclusion: There were behavioral differences of studied neonates after phototherapy related to their habituation, social interactive, motor response, state organization, state regulation and reflexes. Recommendation: NBAS must be used as a tool in the routine care for neonates with jaundice undergoing photother-apy and establishment of health educational instruction for all working nurses in NICUs about appropriate nursing care to minimize the potential side effects and complications of phototherapy.