A limited number of publications have identified risk factors for Corona Virus Disease 2019 (COVID-19) among Healthcare Providers (HCPs). We aimed to assess the clinical and epidemiological characteristics and the predicting factors related to COVID-19 among HCPs in Egypt. A comparative cross-sectional study was conducted among HCPs via an online questionnaire. Out of 440 responses, a total of 385 complete responses were analyzed. The responders’ mean age was 37.5±9.4 years, 215 (55.8%) of the participants were males. They included 77 (20%) confirmed COVID-19 cases; most of them had mild (58.6%) or moderate symptoms (30%), and (9.1%) were asymptomatic. Almost all sustained infection while on duty (97.4%). The sources of infection were either infected patients (39%), colleagues (22.1%), household contacts (5.2%) or uncertain (33.8%). The sources were symptomatic in only 62.3% of cases. Asymptomatic or pre-symptomatic sources accounted for 37.7% of the cases. Exposure occurred during healthcare provision in 66.3% of the cases. The presence of co-morbidities (OR = 2.53, CI 1.47–4.38, P = 0.001), working more than 8 hours per day in isolation hospital (OR = 3.09, CI 1.02–9.35, P = 0.046), training on hand hygiene (OR = 2.31, CI 1.05–5.08, P = 0.038) and adherence to IPC measures (OR = 2.11, CI 1.16–3.81, P = 0.014) were the significant predictors of COVID-19. In conclusion, COVID-19 occurred in 20% of responders. Silent spread from asymptomatic or presymptomatic patients, and infected colleagues in hospital settings is an alarming sign. Proactive infection prevention and control measures are highly encouraged on both strategic and operational levels. Reconsideration of surveillance strategy and work-related regulations in healthcare settings are warranted.