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Background: Congenital anomalies (CA) of the Central Nervous System (CNS) are birth defects of the physical structure of the brain or spinal cord that occur during fetal intrauterine growth, some are caused by genetic factors and other by environmental factors. This study aimed to: Assess the nurses’ competency level regarding the care of infants with congenital anomalies of central nervous system. Design: A descriptive study was used to conduct this study. Setting: This study was conducted at Neurosurgery Department at Mansoura University Hospital. Subjects: A purposive sample composed of all available nurses (55 nurses), which are working at the previously mentioned setting. Tools for data collection: First tool: Pre-designed questionnaire sheet to assess nurses’ knowledge about CA of CNS. Second tool: Competency Checklist to assess nurses’ practice regarding the care of infants with CA of CNS. Third tool: Modified Likert scale to assess nurses’ attitude. Results: More than three quarters of the studied sample were females, and about two thirds of them had less than 5 years in experience. In addition, slightly more than half of them had good total knowledge, more than half of them had incompetent total practice and less than two thirds of them had positive attitude. Also, there was statistically significant difference between the studied nurses’ total level of practice and their age, educational level and years of experience. Conclusion: There was positive correlation between practices of the studied nurses and their total level of knowledge. Also, it was concluded that nurses’ knowledge, practices and attitude affected the nurses’ competency level, in addition to that, characteristics of the studied nurses were considered as factors affecting their competency. Recommendations: Providing health training program at neurosurgery departments about congenital anomalies of central nervous system to raise awareness of the nurses, Developing a simplified and comprehensive protocol including policy and procedure about care of infants with CA of CNS to be distributed on nurses in neurosurgery departments and Further studies should be carried out in other health care facilities to assess nurses’ knowledge, practice and attitude regarding congenital anomalies of central nervous system.