Background: Nurses play a critical role in preventing healthcare-associated infections, including MRSA. Understanding the knowledge, perceptions, and barriers influencing nurses' practices is essential. Knowledge of MRSA epidemiology and transmission motivates program implementation and adherence to preventive measures. This study assessed nurses' perception of methicillin-resistant Staphylococcus aureus (MRSA) prevention in the critical care unit of King Fahad Hospital, Jeddah, Saudi Arabia. Methods: A cross-sectional descriptive design recruited 112 critical care nurses from King Fahad General Hospital, Jeddah, using convenient non-probability sampling. Results: Nurses' perception of MRSA prevention across five domains (severity: 4.12, benefits: 4.58, self-efficacy: 4.07, susceptibility: 3.86, cues to action: 3.80) yielded a total mean score of 4.09. There was no significant difference in perception based on length of experience (p = 0.465). Conclusion: Regular provision of accurate MRSA information and emphasis on infection control and prevention are crucial for nurses, especially those in frequent contact with MRSA patients. While nurses demonstrated sufficient perception of MRSA prevention, inconsistencies across domains indicate the need for expanded education and support to enhance their understanding of preventive measures for managing MRSA patients.