Background: The severe respiratory syndrome coronavirus (COVID-19) pandemic has affected many aspects of life, much vaccine adopted to minimize morbidity and mortality due to COVID-19. Aim: To assess behavior changes after taken second dose of COVID-19 vaccine among students in university of Hail. Methodology: This cross-sectional questionnaire based study involved 350 participants from Hail University, Saudi Arabia. We distributed online questionnaire to determine differences in the protective measures before and after the second dose of COVID-19. Results: We included 350 participants from Hail University in Saudi Arabia in this study. Declines at different levels was detected in all protective measures after the second dose of COVID-19 vaccine that were in the questionnaire compared to before taking the second dose of COVID-19 vaccine. The significance of the behavior changes after receiving second dose of COVID-19 vaccine compared to behavior changes before receiving second dose of COVID-19 vaccine (P<0.0001). Conclusion: the second dose of vaccine resulted noticeable changes in preventive measurement behavior in university of Hail students.