The paper discusses the responses to the COVID-19 crisis in the acute phase of the first wave of the pandemic (February-May 2020) by different Italian regions in Italy, which has a decentralised healthcare system. We consider five regions (Lombardy, Veneto, Emilia-Romagna, Umbria, Apulia) which are located in the north, centre and south of Italy. These five regions differ both in their healthcare systems and in the extent to which they were hit by the first wave of COVID-19 pandemic. We investigate their different responses to COVID-19 reflecting on seven management factors: (1) monitoring, (2) learning, (3) decision-making, (4) coordinating, (5) communicating, (6) leading, and (7) recovering capacity. In light of these factors, we discuss the analogies and differences among the regions and their different institutional choices.