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Introduction: Vaccines are considered preventive measures to reduce coronavirus disease 2019 (COVID-19) spread around the world. There are many factors for adherence and acceptance of COVID-19 vaccination., Objectives: The study aimed to investigate nursing students' knowledge, perception, and factors that influence their adherence to COVID-19 vaccines., Methods: A descriptive cross-sectional study design was conducted among nursing students at the Faculty of Nursing, Mansoura University, Egypt, during the period between September 1 and November 30, 2021., Results: Of the total of 500 participants, 76% took a COVID-19 vaccination. About 89% of participants rated the correct answer related to COVID-19 vaccination. Obligatory to enter the faculty, protect family and friends, and protect myself were the most reasons of adherence (80.3, 73.7, and 70.8%, respectively) while fear of adverse events and lack of information about vaccine were the most reasons of nonadherence (87.5 and 79.2%, respectively) to COVID-19 vaccination. The majority of participants (62%) had expressed positive perception toward COVID-19 vaccination. Education level, training program about COVID-19, previous infection with COVID-19, perception toward COVID-19 vaccination, and knowledge toward COVID-19 vaccination were significantly ( p    =   .035, p    =   .027, p    =   .009, p    =   .008 and p    =   .033, respectively) associated with students' adherence to take COVID-19 vaccines., Conclusion: Accurate knowledge and perception about COVID-19 vaccines are the stronger predictors of vaccine hesitance or acceptance among nursing students in Egypt. Campaigns to increase knowledge and perception of COVID-19 and its vaccines among nursing students are needed to improve vaccine acceptance and reduce vaccine hesitance., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)