Background: The administration of sedation is an essential part of intensive care. Therefore, nurses must be up-to-date on the latest sedation knowledge and practice, as sedation is associated with serious dangers for patients. The study aim: Explore critical care nurses' knowledge and practices regarding intravenous sedation for mechanically ventilated patients. Design and sample: A cross-sectional descriptive exploratory design was used. A convenient sample of 105 nurses working at critical care units. Setting: The present study was carried out in Critical Care Units. Tools of data collection: Nurses' Knowledge Assessment Questionnaire that included basic knowledge to measure the level of knowledge held by nurses working in critical care units on sedative drugs, and 26 Items Survey Questionnaire to measure knowledge of sedatives, sedation assessment, and management, and nurses' practice observational checklist to assess nurses' practice regarding the administration of sedative medications via syringe pump.Results. 94.3% of the studied nurses had unsatisfactory knowledge regarding basic knowledge, while, 89.5% had unsatisfactory regarding sedation assessment and management. 73.3 % of nurses had incompetent practice regarding the administration of sedative medications. Also, regarding practice areas, the majority of nurses' practices regarding the preparatory phase, Propofol administration, ketamine& midazolam administration, general administration, and post-procedure phase was incompetent with percentage 100 %, 91.4% 84.8%,84.8%.75.2%, and 69.5 % respectively. There was a statistically positive correlation between nurses 'basic knowledge and total nurses 'practice regarding the administration of sedative medications with r=.263 and P value .02*. Conclusion: The majority of nurses had an unsatisfactory level of knowledge regarding intravenous sedation. Also, the majority of nurses had an incompetent level of practice regarding intravenous sedation. Recommendations: Educational nursing guidelines regarding intravenous sedation should be conducted.