Since November 1st, 1809 it has been the parish church of the Catholic community of the Holy Spirit.
Elector Johann Wilhelm died in 1716. His brother and successor Karl Philipp argued with the Reformed Council of Churches about the 80th question of the Heidelberg Catechism and about the nave of the Heiliggeistkirche, as a result of which the Elector moved his residence and government to Mannheim in 1720. It was not until 1749 that construction work could be resumed thanks to the generosity of Elector Karl Theodor (1742-1799). The nave was already covered in the following year, and in 1751 the facade and the vault were completed. However, the work dragged on until late autumn 1759. The Mannheim court architect Franz Wilhelm Rabaliatti (1716-1782), who at the same time built the seminarium Carolinum for the Heidelberg Jesuits, was in charge of construction. After the abolition of the Jesuit order in 1773, its tasks and institutions were taken over by the Lazarists from 1782 to 1793. In the following years the church served as a hospital. Since November 1st, 1809 it has been the parish church of the Catholic community of the Holy Spirit.
The baroque furnishings are no longer preserved today. The altar painting by the Kaulbach student Andreas Müller has been preserved. The Elector Frederick the Victorious is buried in a crypt in the northeast corner of the church. To the east of the church portals is the entrance to the former Jesuit college. Originally, the facilities of the Jesuits comprised a grammar school (today the Philosophical Seminary) and the Carolinum seminar, which is now used by the university administration.