BackgroundIntensive care units (ICUs) had to rapidly adapt infection prevention and control (IPC) practices during the coronavirus disease 2019 (COVID-19) pandemic.ObjectivesTo determine ICU nurses’ COVID-19 IPC-related knowledge, attitudes, practices, and perceptions.MethodA mixed-methods study was conducted at the Groote Schuur Hospital ICU, Cape Town, South Africa (20 April 2021 and 30 May 2021). Participants completed anonymous, self-administered, knowledge, attitudes and practices (KAP) questionnaires. Individual interviews were conducted regarding nurses’ lived experiences and perceptions of COVID-19 IPC in critical care.ResultsIn total, 116 ICU nurses participated (93.5% response rate) including 57 professional nurses (49%), 34 enrolled nurses (29%) and 25 enrolled nursing assistants (22%); young females (31–49 years) predominating (n= 99; 85.3%). Nurses’ overall COVID-19 IPC knowledge scores were moderately good (78%); professional nurses had greater knowledge of COVID-19 transmission (p< 0.001). Intensive care unit nurses’ attitude scores towards COVID-19 IPC were low (55%), influenced by limited IPC training, insufficient time to implement IPC and shortages of personal protective equipment (PPE). Respondents’ scores for self-reported COVID-19 IPC practices were moderate (65%); highest compliance rates were for hand hygiene after touching patient surroundings (68%). Only 47% ICU nurses underwent N95 respirator fit-testing despite working in a COVID-19 ICU.ConclusionRegular COVID-19 IPC training is needed to equip ICU nurses with the knowledge and skills to prevent healthcare-associated COVID-19 transmission. Enhanced IPC training and consistent PPE availability may support more favourable attitudes and better IPC practices. Comprehensive IPC and occupational health support should be offered to ensure ICU nurses’ wellbeing during pandemics.ContributionEnhanced IPC training and consistent PPE availability may support better attitudes and IPC practices.