Background: Central venous catheters (CVCs) are vascular infusion tools utilized for studying hemodynamic variables, dialysis, administration of medication, and nutrition. Catheter related blood stream infection (CRBSI) is a complication of central venous catheter (CVC) use. Central venous catheter-related infection (CVC-RI) is considered a common cause of increased morbidity, mortality, and medical care costs in intensive care units (ICUs). Aim of the study: to assess nurses' performance regarding infection control measures for patient with central line in critical care unit. Research design: A descriptive exploratory design was utilized. Subjects: Purposive sample of critical care nurses working in the ICU, at El-Fayoum University Hospital, 40 nurses from both genders, with different ages, educational levels and years of experience were selected for this study. Tool: Data were obtained through three main tools; Nurses' Self-administered questionnaire, Nurses' observational checklist and Nurses' attitudes questionnaire tool. Results: this study revealed that about more than two thirds of studied nurses had unsatisfactory knowledge and practice regarding infection control measures related to central line. Also, about (77.5%) of them had negative attitude regarding infection control measures for patient with central line. There were statistically significance correlation between nurses' level of knowledge, practice and their attitude .there were statistical significant relations between nurses' performance and their socio-demographic characteristics as regards age, education and experience Conclusion: Nurses had unsatisfactory level of knowledge, practice and negative attitude regarding infection control measures related to central line. Knowledge, practice &attitude were found to differ significantly in relation to socio-demographic data. Recommendation: Designing nurses' infection control program to improve their knowledge and practice regarding infection control measures related to central line. The study should be replicated on large sample & in different hospitals setting in order to generalize the results.