Fatal Opioid Overdoses by Historical and Contemporary Neighborhood-Level Structural Racism.

Importance: Black, Indigenous, and Latino communities are disproportionately affected by the US overdose epidemic. Structural inequalities, encompassing social, economic, and infrastructural dimensions, have been increasingly theorized as fundamental drivers of these disparities. Objective: To investigate whether there is an association between neighborhood-level structural racism and opioid-involved overdose deaths in an urban area. Design, Setting, and Participants: This ecological serial cross-sectional study of 796 census tracts (2017-2019) and 792 census tracts (2020-2022) in Chicago, Illinois, used a geospatial and intersectional analytic approach. A quasi-Poisson spatial regression was conducted to examine associations between neighborhood-level structural racism and census tract-level opioid-involved overdose deaths before the COVID-19 pandemic (2017-2019) and during the COVID-19 pandemic (2020-2022). Eigenvector spatial filtering was used to control for residual spatial autocorrelation. Population density was also accounted for in the regression model. Two structural racism indicators (historical redlining and contemporary racialized economic segregation) were combined to develop an index that captures 4 distinct neighborhood intersectional groups of racism over an 80-year period. Average marginal effect calculations were also performed to support the interpretability of the findings. Data were analyzed from February 19, 2024, to July 3, 2025. Exposure: A combined measure of 2 structural racism indicators (historical redlining and contemporary racialized economic segregation). Main Outcomes and Measures: Overdose deaths were aggregated to census tracts; the main outcome measure was the number of overdose deaths at the census tract-level. Results: The total sample sizes were 796 census tracts before the COVID-19 pandemic (2017-2019) and 792 census tracts during the COVID-19 pandemic (2020-2022). As defined by the study's combined measure of structural racism, census tracts with high levels of racism in the past and/or present showed statistically significantly higher number of fatal overdoses compared with tracts with low levels of racism both in the past and present. Just before the COVID-19 pandemic (ie, 2017-2019), tracts with high sustained levels of structural racism past and present had, on average, over 2 more fatal overdoses per tract compared with sustained advantaged tracts (average marginal effect, 2.60; 95% CI, 2.02-3.19; P < .001). During the COVID-19 pandemic (2020-2022), tracts that were advantaged in the past but experienced high present-day segregation had, on average, almost 4 more fatal overdoses per tract compared with sustained advantaged tracts (average marginal effect, 3.81; 95% CI, 1.94-5.68; P < .001). The overall burden of overdose death was higher for all neighborhood groups during the pandemic compared with before the pandemic. Conclusions and Relevance: These findings provide preliminary evidence that structural racism could be a root cause of opioid-involved overdose deaths. Future research is needed to identify mechanisms linking structural racism to overdose deaths and to develop effective policies and programs to reduce fatal overdose rates.