The contextual predictors of mortality in the United States are well documented, but the COVID-19 pandemic may have upended those associations. Informed by the social history of disease framework (SHDF), this study examined how the importance of county contexts on adult deaths from all causes, drug poisonings, and COVID-19-related causes fluctuated during the pandemic.

Using 2018 to 2021 vital statistics data, for each quarter, we estimated associations between county-level deaths among adults ages 25 to 64 and prepandemic county-level contexts (economic conditions, racial-ethnic composition, population health profile, and physician supply).

The pandemic significantly elevated the importance of county contexts—particularly median household income and counties’ preexisting health profile—on all-cause and drug poisoning deaths. The elevated importance of household income may be long-lasting. Contextual inequalities in COVID-19-related deaths rose and then fell, as the SHDF predicts, but rose again along with socio-political disruptions. The findings support and extend the SHDF.