BACKGROUND: In the intensive care unit (ICU), infections due to multidrug-resistant (MDR) bacteria lead to poor clinical outcomes, prolonged ICU and hospital stays, high mortality and morbidity rates, and higher patient care cost. This study investigated knowledge, attitudes and practices (KAP) of ICU head nurses in Iran towards infection prevention and control (IPC) measures and antimicrobial resistance (AMR). METHODS: This study was conducted among 61 ICU head nurses of the 36 hospitals in Isfahan, Iran on 19th July 2023. Data was collected by self-administer questionnaires. Data analysis was performed using SPSS version 25.0 level of significance was considered to be less than 0.05 in all tests. RESULTS: Of the 61 participants, 56 (91.8%) were female and their ages ranged from 27 to 56 years old with a mean age of 39.3 ± 5.6 years. 75.4% of participants had a bachelor's degree and 24.6% had a master's degree. The mean work experience in the ICU and duration of experience in the hospital was 8.1 and 16.2 years, respectively. The mean scores for KAP were 3.84 ± 1.86 (with a range of 0-9), 55.00 ± 12.50, 35.84 ± 4.19 (with a range of 24-48) and 21.27 ± 3.13 (with a range of 17-29), respectively. There was a significant relationship between knowledge and total years of experience (r = 0.256, P <
0.048). CONCLUSION: The study showed that most participants had weak knowledge, a positive attitude and weak practices. Consequently, more emphasis is needed to improve the ICU head nurses' KAP toward IPC measures and AMR, especially in areas where gaps were identified. Additionally, there is a need to an educational plan on these topics in the training of nursing programs.