Background: Patients with compromised or non-functioning gastrointestinal tracts (GITs) may be fed through a line implanted in a vein, a procedure known as parenteral nutrition (PN). Objective: This study aimed to assess critical care nurses' knowledge and practices regarding care of patients undergoing total parenteral nutrition.   Subjects and methods: A descriptive exploratory design was utilized to achieve the aim of this study.The study was conducted at Intensive Care Unit of Tanta University Hospital.A convenient sample of all available nurses (50 nurses) from both sex were included in the study. Two tools were used in this study: Self-administered interview questionnaire and observational checklist to assess nurses' practice regarding care of patients undergoing total parenteral nutrition (TPN). Results: 52% of the studied nurses their mean age was 31.56 ± 8.56 years. 56 % of the studied nurses attended training courses regarding care of patients with TPN. 82% of them had unsatisfactory level regarding total knowledge level, 84% of them had incompetent practice level regarding caring of patients with TPN. There was statistically significant relation between total level of nurses' knowledge and their gender and there was no statistically significant relation between total level of nurses' practices and their demographic characteristics. Conclusion: A positive and statistically significant relationship was found between nurses' levels of overall knowledge and the level of care they provided to patients.