At the beginning of the war, this concert hall from the nineteenth century underwent reconstruction. But when the restored hall was reopened on 20 May 1941, the German occupying forces made frequent use of the building and its facilities. In early November 1941, for example, a large meeting of the so-called Arbeitsbereich of the Nazi Party (NSDAP) in the Netherlands was held, at which Seyss Inquart, among others, spoke. In January of the following year, a concert was organised for the Winterhulp (Winter Relief), a propaganda campaign set up by the NSB based on German ideas to collect money to buy goods for poor people to help them through the winter. In April, a large ceremony was organised to induct boys and girls aged 10 into the Hitlerjugend and the Bund der Deutsche Mädel. The timing of the event was so planned that it fell on the evening before Hitler's birthday. In October 1942, another NSDAP meeting was held in the Musis Sacrum with Seyss Inquart in attendance. Anton Mussert of the NSB also attended meetings in this building. This is how the war continued.

Besides being a building for meetings of the occupying forces, this building was also used by the Germans as a recreational building, a so-called "Wehrmachtsheim". German soldiers could go here to relax with, among other things, film showings and performances.

During the Battle of Arnhem Musis Sacrum was given a completely different function. Because of the design of the building and the proximity of the combat zone around the bridge, captured Britons were assembled here from Tuesday 19 September 1944. Musis Sacrum was not the only building where this happened, also for example in the Eusebius Church, the Walburgiskerk and in the Duivelshuis Brits were kept prisoner. A few days later, when on Thursday 21 September the fighting around the bridge had ended and the British had surrendered, the British soldiers were assembled in the Musis Sacrum and marched off from this assembly point in captivity.