Objectives. To test the hypothesis that deaths of despair, a marker of social suffering, were associated with greater support for Brexit in the United Kingdom’s 2016 European Union referendum.

Methods. We used cross-local authority regression models of Brexit vote shares on changes in suicide and drug-related death rates before (2005–2007) and after the recession (2014–2016), adjusting for sociodemographic factors. The population comprised 345 local authorities in England and Wales.

Results. Mortality rates were associated with voting patterns. An increase of 10 drug-related deaths per 100 000 was associated with a 15.25-percentage-point increase in Brexit votes (95% confidence interval [CI] = 10.27, 20.24), while an increase of 10 suicides per 100 000 was associated with a 9.97-percentage-point increase in vote shares for Brexit (95% CI = 6.25, 13.70). These results were substantially attenuated after we adjusted for education, and reduced to nonsignificance for drug mortality (b = 2.18; 95% CI = –0.21, 4.57) and suicide (b = 0.94; 95% CI = –0.32, 2.21) upon inclusion of other sociodemographic factors.

Conclusions. Worsening mortality correlated with Brexit votes. These phenomena appear to share similar antecedents. A rise in such deaths may point to deeper social problems that could have political consequences.