In the Easter Season, which starts on Holy Saturday night and concludes with the seventh Sunday of Easter, Pentecost Sunday, the Regina Caeli is one of the four seasonal antiphons that can be chanted or recited to the Blessed Virgin Mary. It is commonly done during Compline (night prayer) during the Liturgy of the Hours. The Regina Caeli is also the prayer that should be chanted or recited in place of the Angelus during the same time frame.

During the late 6^th century, a great epidemic hit the entire city of Rome. In order to combat this paralyzing virus, Saint Gregory asked that a procession of prayer be organized.