In the 16th century, the village of Mellieħa was depopulated due to raids by Barbary pirates, especially after a major attack in 1551. The church therefore ceased to be an independent parish and it was absorbed into that of Naxxar. During the Great Siege of Malta in 1565, the church was reportedly visited by Don García de Toledo, the leader of the relief force which ended the siege. The sanctuary's dedication was subsequently changed from the maternity of Mary to the Nativity of Mary.