Background: Spinal cord injury is a debilitating and irreversible injury leading to complete or incomplete loss of sensory and motor function. Knowledge, practice and attitude of nurses can significantly affect the outcomes of patients. Objective: This study aimed to assess nurses' performance regarding care of patients with spinal cord injury. Patients and methods: Design: A descriptive exploratory design was utilized. Setting: The study was conducted at Neurosurgical Intensive Care Unit and Neurology Care Department at Fayoum University Hospital. Sample: A convenient sample of all available nurses (90 nurses). Tools: Three tools were used: I) Self-administered questionnaire. It included two parts: demographic characteristics of the studied nurses and nurses' knowledge. II) Nurses' practices observational checklist. and III) Nurses' attitude regarding care of patients with spinal cord injury. Results: Demonstrated that the majority and the most of the studied nurses had unsatisfactory level of knowledge and incompetent practices regarding care of patients with spinal cord injury respectively. While, the most of them had positive attitude. Conclusion: The current study concluded that there was a statistically significant positive correlation between total knowledge scores of the studied nurses and their practices. Recommendation: Providing a well-organized training program to improve nurses' knowledge and practices regarding care of patient with spinal cord injury.