Santo Spirito dei Napoletani is a Roman Catholic church on via Giulia, in the Regola rione of Rome.

By 1572 the church was in a poor state - that year, it and the monastery were assigned to the Confraternity of the Holy Spirit of the Neapolitans.

It was the burial place of Francis II of the Two Sicilies, his wife Maria Sophie and their three-month-old only daughter Cristina.

It was also the national church for the Kingdom of the Two Sicilies from 1934 until 1984, when the three royal burials were transferred to Santa Chiara in Naples.

The church was closed for thirty years due to water leaks and its abandoned state, but was restored in the 1980s and reopened for worship in 1986.