The church stands on the site of King
Ine of Wessex's
Schola Saxonum, or "Saxon School", a charitable institution for
West Saxon pilgrims. According to
Roger of Wendover, Ine founded the Schola Saxonum in AD 727. It included a hostel and a chapel dedicated to Santa Maria. In
mediaeval times a substantial number of pilgrims from Wessex, including fighting men, traveled the
Via Francigena from Canterbury to Rome. The hospice and church were gutted by fire in 817, were sacked by Muslim raiders in 846, and were again burned in 852. It was rebuilt in the 12th century and subsequently restored several times. In 1475
Pope Sixtus IV commissioned joining the church to the nearby Hospital of the Holy Spirit for
foundlings (which
Pope Innocent III had built and whose history is given in wall-paintings in the church's sacristy) and given a
bell tower. In 1538–1545,
Antonio da Sangallo the Younger, or
Baldassare Peruzzi, rebuilt the church after it had been damaged during the
Sack of Rome. An organ, which survives, was added in 1547. In 1585–1590,
Pope Sixtus V had the exterior restored, giving the church its present façade by
Ottavio Mascherino, inspired by a design of Sangallo. This facade has two stories, with
Corinthian pilasters dividing the lower one into five sections, and the upper divided into three sections. In the upper middle section is a circular window, and above that is the coat-of-arms of Pope Sixtus V. The façade is crowned by a
pediment. It is a typical example of
Renaissance architecture. In the stational procession for the first Sunday after the Octave of the Epiphany, instituted by Pope Innocent III (1198–1216), a procession carried the veil of
Saint Veronica from
Saint Peter's Basilica, and the Pope celebrated Mass in this church. Indulgences were granted to those who took part, and money was distributed to the poor. The inscriptions found in Santo Spirito in Sassia, a valuable source illustrating the history of the church, have been collected and published by Vincenzo Forcella. ==Art and architecture==