Respiratory distress syndrome (RDS) considered one of the most serious disorders which leading to high morbidities and mortalities among neonates. It occurs when a neonate's lungs aren't fully developed and unable to gain enough oxygen. The aim of this study was to determine the effect of clinical pathway on nursing care of neonates with respiratory distress syndrome. A quasi-experimental design was used. This study was carried out at neonatal intensive care units affiliated to Benha University Hospital and Benha specialized hospital of children and Benha Teaching Hospital at Benha city. A convenient sample of (150) nurses and all the available neonates with respiratory distress syndrome (150 neonates). Three tools were used;ToolI- A structured interviewing schedule, which consists of four parts: Nurses' characteristics, neonates' characteristics, Nurses' knowledge regarding neonatal respiratory distress syndrome, and Nurses' Knowledge about nursing care of neonates with Respiratory distress syndrome. Tool II- Clinical pathway of care checklist. Tool III-Neonatal clinical outcome assessment sheet. Results of this study revealed that, there was statistically significant differences regarding the effect of clinical pathway on the clinical outcomes of studied neonates pre and post clinical pathway implementation. This study concluded that: Implementation of the clinical pathway improved nurses' knowledge and practice that reflecting obvious improvement in clinical outcomes of neonates with respiratory distress syndrome. The study recommended that Clinical pathway on nursing care of neonates with respiratory distress should be applied for neonates with respiratory distress at different settings.