Aim: This study aimed to identify factors affecting knowledge and practice of infection prevention and control (IPC) among healthcare workers (HCW) during COVID-19 outbreak in Nigeria.Method: An online sample of 402 Nigerian HCW was recruited in April, 2020 via their social media closed user group chats. Data was collected online using questionnaire that was adapted from the study by Melaku et al. Data analysis was done with computer software IBM SPSS version 20.0.Results: Three hundred and thirty-one (82.3%) had good knowledge of IPC while only 230 (57.2%) had good practice of IPC. Age group (p<0.001), profession (p=0.005), type of health facility (p=0.014) and IPC training (p<0.001) were significantly associated with the knowledge of IPC while sex (p=0.005), profession (p=0.009), type of health facility (p<0.001), IPC training (p<0.001) and availability of water in health facility (p=0.014) were significantly associated with the practice among the HCW. After multiple logistic regression analysis, age group, type of health facility and IPC training remain significant predictors of knowledge while sex, type of health facility, IPC training and availability of water in the health facility remain significant predictors of practice of IPC among HCW.Conclusion: Secondary to these findings, regular IPC training of HCW and making sure water is always available at health facilities was suggested. This study also recommends that special considerations should be given to males, older and primary health facilities HCW in order to improve their knowledge and practice of IPC which is important in limiting infections among them.