Vaccination against COVID-19 is one of the highly effective preventative strategies to reduce morbidity and mortality associated with COVID-19 infection. The rapid approval of COVID-19 vaccination due to the raging pandemic, media coverage, anti-vaccination groups, and concerns about adverse effects associated with vaccination has given rise to COVID-19 vaccine hesitancy. Current evidence suggests that psychosomatic and nocebo-related adverse effects account for a significant proportion of common adverse effects following COVID-19 vaccination. The most common adverse effects are headache, fatigue, and myalgia, which are highly prone to nocebo effects. In our review article, we discuss the role of psychosomatic and nocebo effects in COVID-19 vaccination-related hesitancy, predictors of such effects, and strategies to reduce vaccine hesitancy. General education regarding psychosomatic and nocebo effects and specialized education for at-risk populations may reduce psychosomatic and nocebo-related adverse effects following COVID-19 vaccination, ultimately reducing hesitancy.