Objectives: To evaluate the knowledge, attitude, and acceptance of COVID-19 vaccine among the general population of Oman, on the eve of the rollout of vaccination program in the country. Methods: A cross-sectional study was conducted using a structured and validated online questionnaire. Adults residing in Oman were invited to participate in the study between 22 and 24 December 2020. Logistic regression analysis was used to identify the factors associated with COVID-19 vaccine acceptability. Results: Of the total of 966 participants, the majority (612; 63.4%) were women. Most participants were younger than 40 years (572; 59.3%). Participants displayed good awareness about COVID-19 (946; 97.9%) and the global vaccine development initiatives (831; 86.0%). Only 265 (27.4%) participants were willing to get themselves vaccinated. The majority were either uncertain 365 (37.8%) or unwilling 336 (34.8%). The main driver of vaccine acceptance was to protect oneself and others (186/265; 70.0%). The main reasons given for vaccination hesitation/refusal were concerns over possible side-effects (505/701; 72.0%), safety concerns (386/701; 55.0%), and ineffectiveness of the vaccine (107/701; 15.3%). Conclusions: On the eve of the first-ever rollout of COVID-19 vaccine in Oman in December 2020, the surveyed residents of the country expressed significant hesitancy to get themselves vaccinated. Participants' perceptions of risk of contracting COVID-19, their trust in vaccines, government, and their health system were important predictors of vaccine acceptance. These results enabled development of strategies to address such concerns to facilitate vaccine acceptance among the residents of Oman. The results of this study can be used by researchers to conduct comparative research in future, with more emphasis on Omani youth (< 40 years).