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The experience of social withdrawal may potentially lead to the misuse of prescription drugs to manage negative experiences. Social withdrawal among young adults has become an increasing problem; this was exacerbated within the context of the COVID-19 pandemic. We examine trajectories of social withdrawal and prescription drug misuse among young adults across the years spanning the pre- and post-pandemic period. Using nationally-representative National Survey on Drug Use and Health data from 2017-2023, we use binary logistic regression models to examine the relationship between social withdrawal and prescription drug misuse, net of mental health, by assessing any misuse of prescription drugs as well as misuse of four classes of prescription drugs – opioids, tranquilizers, stimulants, and sedatives. We also examine the temporal trend to see whether the pandemic period brought on changes, including trends in prescription drug misuse by experiences of social withdrawal. Accounting for covariates, a one-unit increase in social withdrawal is associated with higher odds of any misuse (AOR=1.024), misuse of opioids (AOR=1.030), tranquilizers (AOR=1.033), and sedatives (AOR=1.110), but not stimulants. Across all forms of misuse except stimulants, the gap between socially withdrawn and non-withdrawn young adults shrank over time. A decline in misuse of all drug classes occurred, starting prior to the pandemic onset and stabilizing afterwards. We find that an association exists between social withdrawal and prescription drug misuse among young adults, but the relationship diminished after the onset of the pandemic. The pandemic’s disruption of social routines may have made socially withdrawn and non-withdrawn young adults, at least temporarily, more similar.