Background: Acceptance of coronavirus disease 2019 (COVID-19) vaccine is uncertain, and uptake of the vaccine may be hampered by the widespread reduction in public trust in immunization. Uptake of 55–82 percent is needed to gain herd immunity against COVID. Thus, investigating important Health belief model (HBM) components that impact the COVID-19 vaccination may be critical for interventions designed to improve vaccine acceptability. Objectives: To assess the acceptance of COVID-19 vaccine among Egyptians and its determinants based on the Health belief model Methods: A cross-sectional study was conducted among 1152 Egyptians, information was collected in two ways: a face-to-face interview in outpatient clinics, Faculty of Medicine, Zagazig and Cairo Universities and through social networking sites, including Facebook and WhatsApp between May and June 2021. Results: Overall, 37.5% accept to receive the vaccine, and those who plan to get the COVID-19 vaccination believe it is a more serious illness, are more susceptible to the disease, have a higher perception of infection risk, perceive more benefits from vaccination, and greater levels of cues to action and self-efficacy as well as reduced perception of barriers concerning the vaccine. Individuals perceived COVID-19 as a more serious illness aged 30 or more, female, high school or higher, working, urban residents, married, or chronically ill. Conclusions: Egypt has one of the lowest rates of COVID-19 vaccination acceptance, since vaccination appears to be the only method to stop the pandemic, the factors associated with low vaccine acceptance must be addressed.