The majority of neonates, premature, and low birth weight infant vulnerable to respiratory problem and complications. Continuous Positive Airway Pressure (CPAP) is a means of providing respiratory support to neonates with either upper airway obstruction or respiratory failure. Respiratory failure constitutes either failure of ventilation or failure of lung function. The study aimed to evaluate the effect of educational guidelines program about nursing care of neonates receiving continues positive airway pressure. The study utilized a quasi-experimental research design. The sample consisted of all (80) nurses and (160) neonates they were assigned to the study using a consecutive sample. The study was conducted in the neonatal intensive care units at Benha Specialized Pediatric Hospital. The required data were collected using the following three tools, tool (I) self-administered questionnaire sheet, tool (II) Nurses’ knowledge regarding CPAP device and tool (III) clinical practice guidelines of CPAP. The study results revealed that nurses who received the educational guidelines program demonstrated a statistically significant mean score of knowledge and practice. Recommendation: A training program for nurses working in neonatal intensive care units with continuous updates in their knowledge and practice regarding neonatal CPAP.