Introduction: Nurses are among the most occupationally exposed groups to Corona Virus Disease -19 (COVID-19) infections and their protection is crucial. Currently, many types of vaccines are developed but there are still many issues related to their acceptance among different occupational groups. It is vital to investigate this issue for clarification of the problem and timely targeting of its roots, particularly among the highly exposed workers. Aim of Work: To estimate the level of vaccine acceptance among a group of nurses in Mansoura University Hospitals, Egypt, and to shed the light on vaccines acceptance associated factors, and the reasons for non-acceptance. Materials and Methods: This is an observational descriptive cross-sectional study that was conducted on 262 nurses working in Mansoura University Hospitals, Egypt, during the year 2021. Data were collected using an anonymous self-administered questionnaire. Vaccines' acceptance was questioned, and the reasons for not accepting the vaccines were ascertained. Results: Only 22.1% of nurses in Mansoura University Hospitals accepted to be vaccinated (4.2% already vaccinated and 17.9% are willing to take the vaccine) especially those with self-reported good health status [adjusted odds ratio (AOR) = 3.5 (1.5-8.1)]. The independent predictor on logistic regression is good/fair self-rated health with AOR= 3.5 (1.5-8.1). Concerns about vaccines safety and side effects were the most reported reasons for non-acceptance of vaccination. Vaccine safety concerns and distrust issues were reported. Conclusion and Recommendations: Being a male, previously infected, with good or fair self-rated health were associated with more vaccine acceptance .Nurses' education and increasing awareness are required to correct misinformation about different types of COVID-19 vaccines and improve acceptance of nurses to vaccination. This would be a crucial preventive strategy that targets a highly exposed occupational group. This can be accomplished via health education sessions and increasing workers' motivation towards vaccination.