Over six million individuals have died as a result of the infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that causes Covid-19. The first COVID-19 vaccines were introduced to the public in 2020 through emergency authorizations. This study aims to uncover the fears and misconceptions behind the hesitation or refusal of taking the COVID-19 vaccine in Syria. Methods: Through a nationwide cross-sectional study, a convenience sample of 10006 participants who were at least 18 years old and living in Syria participated in a validated questionnaire during the period between January and May 2022 Results: The majority of recruited individuals were female (n= 6048; 60.4%) from the (18-24) age group (n= 5908; 59%). We recorded 5811 (58%) participants who still have fears and anxieties about the COVID-19 vaccine. The main concerns about vaccines were the rapid development of vaccines (41.4%), fears of blood clots (37.9%), the fears of common side effects (35.2%), and allergic reactions (26.5%). Conclusion: The COVID-19 vaccine is considered the most promising measure for controlling the spread of infection. The success of this policy will depend on the rate of global acceptance of the vaccine. High variability in vaccine acceptance and high vaccine hesitancy can affect the efforts to terminate the COVID-19 pandemic. Addressing the barriers associated with the acceptance of COVID-19 vaccination will be the cornerstone to achieving maximum vaccination coverage. The most common reasons behind refusing the vaccine in Syria were fear of side effects, followed by fears, general concerns, manufacturing-related reasons, and conspiracy belief