Background: In 2019, World Health Organization considered COVID-19 vaccination a global health threat. Vaccine hesitancy is a behavior with delay in acceptance or refusal of vaccines despite available services. The psychological wellbeing of the individuals, such as anxiety or depression, could also affect their acceptability of the new vaccine. The present study aimed at evaluating the COVID-19 vaccination hesitancy and psychological health among the general population in Saudi Arabia. Methods: A cross-sectional study using a self-administered online, close-ended questionnaire was conducted among the general adult population from all regions of Saudi Arabia . The questionnaire included sociodemographic data, the 5C tool to measure vaccination hesitancy, Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7). Data were collected, tabulated, and analyzed using the Statistical Package of Social Science (SPSS) program, version 26. Results: In this study, we collected data from 2543 adults in Saudi Arabia, where 53 % were males. According to PHQ-9, we found that 68.7 % of the participants reported a degree of depression, and GAD-5 showed that 27.2 % had mild anxiety, 19.5 % had moderate anxiety, and 6.8 % had severe anxiety symptoms. The mean confidence constrains, complacency, calculation, and responsibility scores among the participants were 4.91, 3.07, 3.34, 509, and 5.14. Conclusion: The results of the current study showed moderate to good acceptance of the COVID-19 vaccination among individuals in Saudi Arabia. Moreover, this study reported a significant relationship between depression/anxiety and vaccination hesitancy.