The Lodewijks Kerk (Church of St. Louis) was the chapel of a hospice founded in the 15th century, the St. Jacobs Gasthuis. The St. Jacobs Broederschap (Brotherhood of St. James) that operated it was made up of people who had returned from a pilgrimage to Santiago in Spain. Their hospice was not a hospital but probably served as a place to stay on the pilgrimage from northern Europe to Santiago. Leiden, like many other cities, also had a Jerusalem Chapel, maintained by citizens who had returned from a pilgrimage to the Holy Land. There was a Roman Brotherhood as well. The present St. Jacobsgasthuis Chapel was finished in 1538. Changes in devotional habits combined with wars to interfere with pilgrimage routes; interest and practice declined. The St. Jacobsgasthuis was transferred to the administrators of poor relief in 1547. In 1566 the city used the space to store artworks removed from the churches after the iconoclastic rioting. Then the chapel became a guild hall. While the Pilgrims lived in Leiden, cloth was brought here for inspection and quality control and to be sold.

Catholic religious life continued in Leiden after the Reformation. Monks and nuns who had not already fled were not forced to leave. Instead they were granted pensions and forbidden to take in new members. Leiden's 16 convents and monasteries closed. Forbidden to have visible churches, Catholics worshipped in "hidden" churches in attics of private houses. There were eight by the end of the 17th century. The amount of toleration was variable, and at times Catholics were oppressed with fines. (No doubt the Pilgrims were offended that Catholics were tolerated at all.) Within the Catholic world, there were Roman Catholics and "Old Catholics," a denomination formed when a pope in 1702 secretly appointed the pastor of one of Leiden's hidden churches to be Bishop of Utrecht, bypassing traditional rights of nomination that had been granted to Dutch Catholic authorities in the middle ages. Traditionalists remained true to their established privileges, resulting in a continuation of the ancient Dutch Catholic church eventually (since 1723) no longer subordinate to Rome and now in full communion with the Anglican churches. The Old Catholic chapel on the Hooijgracht was taken down and a new church built in 1925. The baroque altarpiece with its painting of the Adoration of the Magi by Willem van Ingen is preserved with other fittings from this secret house chapel in the Municipal Museum "De Lakenhal."

In 1807 a boat moored near the St. Jacobs Gasthuis, loaded with gunpowder, exploded. Several square blocks of houses were destroyed. The chapel was on the edge of the ruined area, which was visited the day after the explosion by King Louis Napoleon, who participated in rescue efforts. At his insistence, the chapel was restored to Roman Catholic use. In honor of the patron saint of France and, of course, in honor of King Louis Napoleon, the chapel was rededicated to St. Louis (Lodewijk in Dutch). This became the first Catholic church in the predominantly Protestant north of The Netherlands that did not have to be a "hidden" church but could openly face the street. It was a symbolic step towards equal rights for Catholics, the 19th-century movement known as Catholic "emancipation."

Soon, in the 1830's, Catholics again built visible churches, often attempting to locate them close to the medieval church buildings whose congregations had become Dutch Reformed. Catholic institutions, - churches, schools, newspapers, trade unions, social clubs, business associations,- were part of a society that developed along strictly separate denominational lines, called "columns." Grocers, clothing stores, marching bands, lawyers, and sports teams, and gymnastic clubs formed around Catholic or Protestant identification, with several sorts of Protestant divisions as well. People within the various groups lived functionally isolated from contact with members of other groups, a situation that has broken down only recently in the face of growing secularization.