A descriptive study was Neonates with central venous catheters constitute a significant group in Neonatal Intensive Care Units. There is no doubt that, adequate care should be applied to them to keep them away from infection. Aim: The study aimed to assess the nurses' performance regarding neonates with central venous catheters. Research design: A descriptive research was used to conduct this study. Research settings: The study was conducted at the Neonatal Intensive Care Units of Obstetric & Gynecological Hospital, Children Hospital affiliated to Ain Shams and Tanta University Hospital. Research subjects: A purposive sample included 60 nurses and 60 neonates with central venous catheters. Tools of data collection: Four tools were used, interviewing questionnaire sheet to assess knowledge, observational checklists to assess practice, and likert type rating scale to assess the attitude. The Results: The study revealed that, nearly half of the studied nurses had poor knowledge regarding central venous catheters, and more than half of them had incompetent practice regarding central venous catheters. Conclusion, Based on the researcher's question, it can be concluded that, the nurses had poor knowledge, incompetent practice regarding central catheters, and had positive attitude regarding central venous catheter care. Recommendations, Implementation of nursing training programs withemphasis and improve nurses' knowledge and practice regarding central venous catheters.