: Background: COVID-19 causes a critical occupational risk to frontline healthcare workers (HCWs) who respond to the pandemic, as they are placed in environments with an increased risk of infection exposure. It is a public health priority to understand how transmission occurs to protect this vulnerable group of HCWs. This study was conducted to estimate the incidence of self-reported COVID-19 infection among physicians and its possible associated factors. Methods: An online national survey using Survey Monkey was initiated to collect sociodemographic e.g. age and sex, occupational e.g. place and duration of work, and clinical data e.g. COVID symptoms and laboratory investigations, and to describe affected physicians' diagnoses. Results: The self-reported incidence of COVID-19 infection was found to be 65.4% among studied physicians. The significant independent predictors of COVID-19 infection were smoking, working as a frontline physician, having contact with a COVID-19 case, and working for less than ten years [ARR (95% CI): 3.0(1.6-5.7), 2.3(1.4-3.8), 2.1(1.2-3.6), and 1.8(1.2-2.9); respectively]. Conclusions: The incidence of COVID-19 infection among Egyptian physicians is relatively high. Smoking, being a frontline physician, having contact with a COVID-19 case, and working for less than 10 years are all factors associated with an increased risk of infection. There should be strict application of preventive measures, periodic screening for COVID-19 for early detection and isolation of infected HCWs together with effective vaccination.