The interior of the church of the former Dominican Convent of San Pablo has an extensive iconographic repertoire of pictorial nature, painstakingly devised by a mentor whose personality has not yet been identified, but who would certainly have been a member of the Order of Preachers.

The Gaditan painter Clemente de Torres (1662-1730), who trained artistically in the workshop of Valdés Leal, is firmly attributed with six of the apostles painted on the pillars of the church, corresponding to Saint Peter, Saint Paul, Saint Andrew, Saint Matthias, Saint James the Less and Saint James the Greater. They are depicted full-length, in solemn and monumental figures, with an emotive spiritual expression. Two other apostles, Saint Philip, and Saint Thomas, reflect the palette of Lucas Valdés (1661-1725), whilethe others belong to an anonymous collaborator of his workshop.

Lucas Valdés's paintings in San Pablo, executed from 1709 onwards, are the culmination of his career as a muralist. There, in the vault of the presbytery, he depicted the Triumph of Faith, demonstrating his mastery of perspective and great compositional mastery in a religious allegorical scene of a certain complexity. In the eight gallones of the intrados of the dome, he painted pairs of angels bearing the attributes of the Lauretan Litany and holding medallions with letters that make up the words Ave Maria. On the Corinthian pilasters attached to the pillars of the transept, he painted a wide repertoire of Dominican saints and blessed. At the top of the side walls of the transept, there are tempera paintings of The Triumphal Entry of Saint Ferdinand into Seville and an auto-da fé in the time of Saint Ferdinand, which are among the best of his work. Another historical scene painted by the same artist, The Battle of Lepanto, reminds us of the wall of the epistle of the institution of the feast of the Virgin of the Rosaryon 7 October 1571 by the Dominican Pope Pius V, coinciding with the naval victory of the Christian armies against the Turks. On the vault of the choir loft , he painted eight scenes from the Old Testament, while on the ceiling of the sacristy he painted The Adoration of the Christ Child in Heaven in the centre, between medallions with The Conversion of Saint Paul and The Apotheosis of Saint Paul.

Lucas Valdés was also the author, around 1710-1715, of the two spectacular canvases that hang on both sides of the main chapel, with the scenes of David and the transfer of the Ark of the Covenant and The rebuilding of the temple of Jerusalem in the time of the prophet Haggai, taken from the Old Testament, and displaying extensive and painstaking architectural backgrounds. But, without doubt, the two most significant oil paintings in the church, from the collection once treasured by the Convent of San Pablo, are those exhibited in the sacramental chapel, where are depicted the episodes of Saint Dominic in Soriano and The Miraculous Healing of the Blessed Reginald of Orleans, which Francisco de Zurbarán (1598- 1664) contracted from the Dominican community in 1626 as part of a larger series, featuring magnificent naturalistic effects, such as the excellent treatment of the textures of the canvases and the varied still-life details. Francisco Pacheco (1564-1644) belonged to an earlier generation, and a beautiful panel of the Virgin of the Rosary with the Souls in Purgatory, executed around 1612, is kept in the parish office. The paintings of Juan de Valdés Leal (1622-1690), which are on display in the chapel of the Quinta Angustia, are fully Baroque, as they were painted in 1659. Furthermore, the interesting canvas that presides over the altarpiece dedicated to the Blessed Souls in Purgatory is correctly attributed to the late Baroque painter Vicente Alanís (1730-1807) around 1772.