Background: Necrotizing enterocolitis is an acquired condition. It is the most common gastrointestinal emergency in the neonatal period and manifested by ischemic necrosis of the intestinal mucosa. Aim of the study was to assess nurses' knowledge and performance regarding care of neonate with necrotizing enterocolitis at neonatal intensive care units. Design: A descriptive research design was utilized in this study. Settings: the study was conducted at neonatal intensive care units of Benha Specialized Pediatric Hospital. Sample: A convenient sample of 60 nurses and 50 high risk neonates had necrotizing enterocolitis were included. Tools of data collection; Two tools were used to collect data: A structured interviewing questionnaire sheet (tool 1) to collect sociodemographic data of nurses and their knowledge about necrotizing enterocolitis, an observational checklist (tool 2) was modified by the researcher to assess nurses' performance regarding care of neonate with necrotizing enter colitis. Results: The present study revealed that; more than two thirds of the studied nurses had an average level of knowledge, two thirds of them, their performance were unsatisfactory and there was a positive relation between total knowledge and performance scores of studied nurses and their personal characteristics. Conclusion: There was a positive correlation between total nurses' knowledge and their performance. Recommendations: Developing training programs regarding care of neonates with necrotizing enterocolitis for the nurses working at neonatal intensive care units is important to improve their knowledge and performance.