Objectives: The study aimed to determine the COVID-19 vaccine acceptance, barriers, and encouraging factors among chronically ill patients in the Qassim population, Saudi Arabia. Method: This cross-sectional study was conducted between July 1, 2021 and March 1, 2022 using a validated and pretested interview-based questionnaire and included adult patients aged 18 years visiting health care centers. A total of 551 responses were included Result: In total, 19.2% of participants suffered from one or more chronic diseases. 27.3% were infected with COVID-19, and 96.2% were vaccinated against COVID-19. The knowledge related to COVID-19 was moderate among our participants (Mean score 12.3 ± 3.0). Participants who were divorced or had higher educational levels had significantly higher knowledge scores (p=0.038, p=0.027). The most strongly agreed-upon barrier factors that increase vaccine receiving hesitancy are concerns about its safety and adverse events. The fear of spreading the sickness to their family was the most common motivator, followed by the lack of adequate vaccination information. Participants who had received the COVID-19 immunization had a substantially higher attitude score (p = 0.005). When compared to non-chronically ill participants, chronically ill patients’ knowledge and attitude toward vaccination exhibited no statistically significant changes. Conclusion: This research gives an early look at Saudi people’s understanding and views concerning COVID-19 vaccinations. The participants mostly report their concerns about vaccination safety and potential adverse effects as a valid explanation for their reluctance to receive the immunization. These findings might help health officials prevent future drops in vaccination rates by increasing public awareness. Key words: COVID-19 vaccines, vaccinations barriers, chronic ill patients, Qassim, Saudi Arabia