The Hospital de la Santa Creu i Sant Pau came into being in 1401 with the merging of six hospitals in the city of Barcelona at that time. Santa Creu, the Hospital of the Holy Cross, as it was called in those days, was right in the centre of the city, in what is now the Raval district, in one of the most important examples of Catalan Civil Gothic architecture.

By the late nineteenth century, due to the rapid growth of Barcelona's population and advances in medicine,the hospital became too small, and it was decided to construct a new building. Thanks to the bequest of the Catalan banker Pau Gil, the first stone of the new hospital, designed by Lluís Domènech i Montaner, was laid on 15 January 1902, though the new facilities would not be opened until 1930.

After eighty years of healthcare activity in the Modernista complex, in 2009 the Hospital de la Santa Creu i Sant Pau moved to new premises built in the north of the precinct, thus commencing a new era for the historic pavilions of Domènech i Montaner.