Background: High number of losses may occur among health care workers (HCWs) who are the key contributors in the COVID-19 battle. Objectives: To explore the baseline knowledge and perception of HCWs who will join working in our isolation unit, correct the wrong believes and investigate their safety at the end of their quarantine period. Method: The study was implemented on 206 HCWs [133 nurses, 28 physicians, 8 pharmacists, and 37 technicians and housekeepers] by assessing HCWʼs knowledge and attitude via on-line questionnaire, improve misconceptions via health care program prior to start their work in the unit and inspect the COVID-19 infection by laboratory and radiological investigations. The inclusion criteria were being HCWs in the isolation unit of COVID-19, National Liver Institute, Menoufia University, Egypt for in the period from of June 10 th to August 10 th , 2020. Results: Base-line questionnaire results revealed good knowledge and positive attitude of HCWs towards 16-COVID-19 items in spite of ignoring the incubation period of the disease. There was significant positive attitude of the HCWs groups, and the total group attitude showed a significant good knowledge score. Health care workers had highly significant good knowledge score and positive attitude towards the importance of training on personal protective equipment (PPE) donning and doffing. Continuous health education on infection control practices and importance of social distancing during the isolation period was emphasized. At the end of the quarantine period, the infection rate was 5.8%. The HCWs with positive SARS-CoV-2 showed negative COVID-Ab results, significant changes in their C-T scan findings and lab findings. Conclusion: Health care workers with good knowledge, perception and who follow strict precautions in an isolation unit are the basis of success in winning the battle against SARS-CoV aiming at keeping HCWs safety with optimum patient care and less harm to the health facilities.