Abstract Events in Catalonia in October 2017 confronted the European Union with an attempt at unilateral secession by a region within an EU Member State. EU institutions and EU Member States have responded by affirming the illegality of the attempted secession and have refrained from attempting to mediate between the Spanish government and the Catalan authorities. This contrasts with the approach of the EU and its Member States in previous cases of unilateral secession occurring within the European space outside the Union, notably the former Yugoslav republics and Kosovo. This article analyses the legal framework and political norms governing the EU’s response to unilateral secession under international and EU law, and considers the prospects for EU-led mediation between Madrid and Barcelona in the future.