Background Individual- and area-level risk factors for suicide are relatively well-understood but the role of macro social factors such as alienation, social fragmentation or ‘anomie’ is relatively underresearched. Voting choice in the 2016 referendum on the UK's membership of the European Union (EU) provides a potential measure of anomie. Aims To examine associations between percentage ‘Leave’ votes in the EU referendum and suicide rates in 2015–2017, the period just prior to, and following, the referendum. Method National cross-sectional ecological study of 315 English local authority populations. Associations between voting choice in the EU referendum and age-standardised suicide rates, averaged for the years 2015, 2016 and 2017, were examined. Results Overall there was a weak, but statistically significant, positive correlation between the local authority-level percentage ‘Leave’ vote in 2016 and the suicide rate 2015–2017: Pearson's correlation coefficient, r = 0.17; P = 0.003. This relationship was explained by populations having an older age distribution, being more deprived and lacking ethnic diversity. However, there was divergence (likelihood ratio test for interaction, χ² = 7.2, P = 0.007) in the observed associations between London and the provincial regions with Greater London having a moderately strong negative association (r = −0.40; P = 0.02) and the rest of England a weak positive association (r = 0.17; P = 0.004). Conclusions Deprivation, older age distribution and a lack of ethnic diversity seems to explain raised suicide risk in Brexit-voting communities. A greater sense of alienation among people feeling ‘left behind’/‘left out’ may have had some influence too, although multilevel modelling of individual- versus area-level data are needed to examine these complex relationships. The incongruent ecological relationship observed for London likely reflect its distinct social, economic and health context.