Background: Sepsis is a global health issue associated with increased morbidity and mortality worldwide. Critical care nurses play a vital role in the early assessment and management of sepsis through applying sepsis bundle. Aim: assess the critical care nursing knowledge and practices regarding sepsis bundle among critically ill patients. Research Design: A descriptive exploratory design was used. Settings: The study was conducted at Intensive Care Units (ICUs) at Fayoum university hospital. Sample: A convenience sample of 30 nurses in the previous mentioned setting. Tools for Data Collection: data was collected by using Sepsis bundle knowledge questionnaire and Nurse's observational checklist. Result: the present study reveals that, 76.7% of studied nurses didn't attend training courses about nebulizer therapy, 46.7% of studied nurses had satisfactory level of knowledge, 33.3% of studied nurses had competent about level of practice. Also, there were highly statistically significant correlation between total score of knowledge of the studied nurse's and their total score of practice. Conclusion: The study revealed that less than half of studied nurses had satisfactory level of knowledge regarding Sepsis Bundle among Critical Ill Patients, while, one third of them had competent level of practice. Additionally, there were highly statistically significant correlation between total score of knowledge of the studied nurse's and total score of practice. Recommendations: Replication of the current study on large sample and different hospitals settings to be able to generalize the results.