The ongoing coronavirus-disease-19 (COVID-19) pandemic had a variable history with differences in its various stages. This study evaluates the status of knowledge, perception, and confidence about COVID-19 preventive measures during the first wave of the COVID-19 pandemic among healthcare workers (HCWs) in Egypt. A cross-sectional study was conducted during the first wave of the COVID-19 pandemic, in July 2020, in Egypt. An-online-based questionnaire was used to collect data. It included items to record demographic data, and an assessment of knowledge, the perception of healthcare facilities preparedness, and HCW confidence about applying infection prevention measures. A total of 465 responses were analyzed. HCWs' mean age was 36.76 ± 9.57 years, 94.2% (n=438) had an adequate level of knowledge, 31% (n=144) had an adequate perception level, and 39.4% (n=183) had an adequate confidence level. The main source of information was international organizations' websites 46.5% (n=216). The main barriers to applying preventive measures were the overcrowding of patient care areas 73.1% (n=339), and limited infection control supplies 68% (n=316). Factors associated with COVID-19 among HCWs were COVID-19 infected family members (OR: 5.86), inability to protect themselves and their families (OR: 5.73), uncertainty about the available hand hygiene supplies (OR: 3.76), male gender (OR: 3.07), and single HCWs (OR: 2.88). Although the majority reported an adequate knowledge level, lower rates of adequate perception and confidence were observed. Revision of preparedness plans in different facilities should be further studied. Psychological support and gender differences should be considered in response programs.