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.