ABSTRACT This article compares the functioning of the intergovernmental systems in Italy and Spain facing the COVID-19 crisis. Combining the public administration literature on policy learning and multi-level governance with that on the institutional collective action framework, this article analyses if and how Italy and Spain have reacted and learned from the external pressures of the pandemic, leading to institutional adjustments to the respective multi-level governance systems in the de-escalation of the first emergency phase. In doing so, the article tests the general hypothesis that the existing political structures and dynamics are a crucial variable to explain the different performance in the pandemic response management. The framework presented in this article could be extended to other countries that follow a federal logic in healthcare provision by public administration scholars who are interested in crisis management studies.