OBJECTIVE This cross-sectional study aimed to investigate vaccine acceptance and attitude to novel coronavirus disease 2019 (COVID-19) vaccine among the general population in Saudi Arabia. METHODS The present study was conducted among the general population in Saudi Arabia above 18 years of age. The data were collected online, by questionnaire containing 20 questions using Google form, in both Arabic and English, and were distributed to friends, families, and relatives through mail, WhatsApp groups, and Twitter. The questionnaire was randomly given out to the people living in five provinces of Saudi Arabia. RESULTS A sum of 1,713 participants responded to the online survey. The greatest number of participants were at the age between 31 years and 45 years (36.6%) and 56.4% were females. The results showed that 74.6% have not registered for the vaccination and 44.9% responded not to take the vaccine. About 60.80% were concerned about the side effects, and 48.2% were worried about the allergic reaction to COVID-19 vaccine. About 49.1% of participants agreed that preventive measures, such as wearing mask, social distance, and using sanitizers, keep the virus away, and 53.20% believes that being exposed to disease naturally is safer for the immune system. Around 23.90% believes that vaccination cannot reduce the possibility of getting COVID-19. CONCLUSIONS In the present study, the negative attitudes and afraid of the side effects of the vaccine are the most reasons for indecision and rejection about COVID-19 vaccine. For the future COVID-19 vaccination campaign not to fail, the Ministry of Saudi Arabia should closely follow the vaccination development processes, inform the public transparently, and consider public's concerns. CONCLUSIONS The results of the current study will help the Ministry of Health in Saudi Arabia to attempt proactive missions by featuring the significance of immunization to the population and empowering vaccine take-up and acceptance.