Background: During triage in the emergency room, observations of vital signs and identification of organ failure are increasingly frequently employed to diagnose systemic inflammatory response syndrome (SIRS) and sepsis. However, there is less emphasis on early detection technologies of systemic inflammatory response syndrome (SIRS) in the critical care unit. Method: This is A prospective research design study, A convenience sample technique utilized consists of (45) nurses working in the intensive care unit at King Khalid general hospital, KSA. Participants completed the electronic questionnaire sheet to assist knowledge of nursing staff about Systemic Inflammatory Response Syndrome by pre, immediate, and post educational program consisting of twenty questions. Results: The findings show a highly statistically significant increase in the mean score in a knowledge level of knowledge before and immediately after the educational program, then it slightly decreases one month after the educational program. There was no statistically significant relationship between the total knowledge of studied nurses and their Sociodemographic Characteristics. Conclusion: Criteria for systemic inflammatory response syndrome (SIRS) are very important to know and, unfortunately, they are not well used in ICU. It is recommended that educational programs be provided for intensive care nurses to help them with the detection of sepsis in the early stages.