BACKGROUND: Since first confirmed case of coronavirus disease (COVID)-19 in December 2019 by Chinese health authorities and subsequent World Health Organization (WHO) declaration that COVID-19 is a global public health crisis, radical changes have occurred all over the world associating massive lockdown with increased numbers of infected cases and related mortalities. As health care workers (HCWs) are at a great risk to get COVID-19 infection and hence can be a dangerous source of spreading it to the community, it was important to assess HCWs knowledge, attitude, and practice toward COVID-19 infection prevention and control (IPC) to help limit the outcomes of COVID-19. AIM: The objectives of the study were to assess the knowledge, attitudes, and practices of physicians regarding COVID-19 IPC. METHODS: Research setting is “Kasr Al-Ainy” Faculty of Medicine, Cairo University Hospital. Design: A cross-sectional analytical observational hospital-based research in June 2020. Population: A convenient sample of 50 physicians working at Cairo University Hospital was included. Data collection: Self-administered questionnaires derived from the WHO IPC guide during health care when COVID-19 is suspected were used. RESULTS: Mean age of studied group was 30.5 ± 3.97, while their mean years of practice were 4.7 ± 3.55. Mean knowledge score among physicians was 5.6 (± 0.56), two-thirds of them had sufficient knowledge regarding COVID-19 IPC as their mean attitude score among 24.9 (± 2.8). While mean practice scores 5.6 (± 1.05), yet only 68% of the participating physicians use a new set of personal protective equipment when care is given to a different patient. CONCLUSION: Physician’s moderate knowledge, poor attitude, and modest practice toward COVID-19 IPC were found to be not sufficient, not favorable nor safe enough to expected standards.