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Syndemics theory has been applied to study interactions between biomedical and social factors leading to the clustering of diseases. Because syndemics theory focuses on interactions that enhance risk, the concept of vulnerability is central to this approach. We conducted a scoping review to better understand how this theoretical framework helped to define, operationalize, and tackle issues of vulnerability during the COVID-19 pandemic. Original research, reviews, and opinion pieces elaborating on syndemics, vulnerability, and COVID-19, published between December 2019 and October 2022 and available from PubMed, were eligible. We analyzed 40 records and identified three framings of syndemics operating during this period: (1) interactions between COVID-19, diseases/health conditions, and specific social factors; (2) interactions between COVID-19 and social determinants of health; and (3) impacts of COVID-19 on specific populations. Emerging conceptualizations described vulnerability to COVID-19 as a systemic issue, explained the impact of COVID-19 control measures on increased vulnerability, and presented COVID-19 as a syndemic on its own. However, this theory's potential for deepening our understanding of vulnerability during this pandemic was constrained by superficial explorations of the interactions between biomedical and social spheres, and insufficient theoretical and methodological support from the social sciences.