Introduction COVID-19 vaccine side effects have a fundamental role in public confidence in the vaccine and its uptake process. Thus far, evidence on vaccine safety has been exclusively obtained from manufacturer-sponsored studies; therefore, this study is designed to assess post-COVID-19 vaccine complications in Makkah province, Saudi Arabia. Method A cross-sectional study included 840 subjects conducted from August to November 2022 to collect data about COVID-19 vaccine side effects. A validated questionnaire was used with 21 multiple-choice items covering demographic data, COVID-19 vaccination type, side effects, and medication used to relieve side effects. The online Raosoft sample size calculator (Raosoft Inc., Seattle, Washington) was utilized for sample size calculation. The Statistical Package for the Social Sciences version 22.0 (IBM Inc., Armonk, New York) was utilized to carry out descriptive statistics. The Shapiro-Wilk test was used to evaluate normal data distribution. Significance of categorized data made by the Pearson's Chi-Squared test and of the vaccination side effects experienced in general wellbeing on a scale of 1-10 by the Kruskal-Wallis test. Result The survey found that most participants in the 18-26 age group were from Jeddah, women, and Saudis. Only 7.1% of participants had comorbidities alone, and 63.1% of participants had previously had COVID-19. The vaccine types used in this study were primarily Pfizer (83.3%), AstraZeneca (9.5%), Moderna (3.6%), and combination vaccines (3.6%). The majority of the participants received vaccination up to the third dose. No side effects were reported by 9.5% of participants, while mild and severe side effects were reported by 90.5% and 23.8% of participants, respectively. Mild side effects included injection site pain, redness, tenderness, or itching (34.5%), fatigue (22.6%), low-grade fever, chills, diarrhea, headache (17.9%), and myalgia (14.3%). Conclusion The majority of the side effects of COVID-19 vaccination were minor reactions (90.5%), but 23.8% were found to be serious side effects, most of which lasted one to three days. More independent studies are needed to investigate gender differences, COVID-19 vaccine efficacy, and the prevalence of side effects in other populations conducted by academic institutions. Additional independent research on vaccine safety is urgently needed to increase public confidence in vaccines and to better understand risk factors for vaccine side effects.