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Background: The assessment of the side effects of the COVID-19 vaccine is crucial to inform individuals about the potential risks and benefits of vaccination and to provide appropriate medical care if necessary. The study aimed to assess the effect of the COVID-19 vaccine on smokers and diabetic individuals and to investigate the occurrence of any side effects in the subpopulation of the Al Jouf region, KSA., Materials and Methods: The questionnaire had three main sections: the first covered basic information including gender, age, general health status, place, socio-economic position, nationality, smoking, and diabetes. Section 2 included the COVID-19 vaccination status and side effects, and the third section dealt with the dental history. Informed consent was obtained from the recruited individuals. Participants completed a Google self-administered questionnaire., Results: One hundred and twenty participants responded to the survey forms. Similarly, for diabetics versus non-diabetics, there was no statistically significant difference in the type of vaccine received (chi-square value = 3.125, p-value = 0.682). For smokers versus non-smokers, the chi-square test showed a non-significant difference in side effects (chi-square = 2.56, p-value = 0.109), indicating that there was no significant difference in the side effects experienced by smokers and non-smokers. For diabetics versus non-diabetics, the chi-square test showed a non-significant difference in side effects (chi-square = 0.34, p-value = 0.560), indicating that there was no significant difference in the side effects experienced by diabetics and non-diabetics., Conclusion: Smokers and diabetics had higher harmful effects than non-smokers and non-diabetics. These findings need larger, robust trials to support treatment decision-making., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hamza et al.)