As COVID-19 spread rapidly during the early months of the pandemic, many communities around the globe anxiously waited for a vaccine. At the start of the pandemic, it was widely believed that Africa would be a significant source of infection, and thus, vaccinating African communities became a primary goal among local and global health authorities. However, when the COVID-19 vaccine became available in March 2021 in Sierra Leone, many people viewed it with scepticism and hesitation. While much literature has focused on access and distribution-related challenges for vaccination in the region, a growing number of studies discuss vaccine hesitancy as driving low vaccine uptake. Shifting attention to understanding the determinants of vaccine hesitancy remains fundamental to increasing vaccination rates, as negative vaccine perceptions tend to delay or prevent vaccination. This study sought to do this by assessing, through semi-structured qualitative interviews, vaccine-related attitudes and experiences of residents of Sierra Leone’s Kono District. In contrast to studies that utilise “knowledge-deficit” models of belief, however, this study drew upon the vaccine anxieties framework (Leach and Fairhead, 2007), which views vaccines as being imbued with personal, historical, and political meaning. Findings suggest that important bodily, social, and political factors, including fear of side effects, the spread of misinformation prompted by poor messaging strategies, and distrust of government and international actors, influenced people’s COVID-19 vaccine attitudes and behaviours. It is hoped that the study’s findings will inform future policies and interventions related to vaccine uptake in Africa and globally.