Similar to most countries, Saudi Arabia faced several challenges during the novel coronavirus disease 2019 (COVID-19) pandemic, some of which were related to the religious position of the country. The main challenges included deficits in knowledge, attitudes, and practices toward COVID-19, the negative psychological impacts of the pandemic on the general population and healthcare workers, vaccine hesitancy, the management of religious mass gatherings (e.g., Hajj and Umrah), and the imposition of travel regulations. In this article, we discuss these challenges based on evidence from studies involving Saudi Arabian populations. We outline the measures through which the Saudi authorities managed to minimize the negative impacts of these challenges in the context of international health regulations and recommendations.