On either side of the Virgin, kneel St. Sixtus and St. Barbara.  Placed also amid the clouds, but below the Madonna, they are near the sovereign mediatrix, as mediators also between the world and the Sovereign Judge.  St. Sixtus is seen on the right in profile, his head is raised towards the Infant Jesus, his left hand is placed devoutly on his breast while his right is foreshortened and points towards the spectator.  He wears a white rochet tied by a girdle with golden tassels, a white amice around his neck, a magnificent pallium woven with gold falling to his feet, and a long chasuble embroidered with gold and lined with red enveloping his shoulders and arms, the wide folds of which are lost amid the clouds.  His head is bare, and his white tiara, adorned with the triple crown, is placed on the balustrade that runs horizontally across the base of the picture.  It is impossible to find a representation of pontifical sovereignty of greater fervour, grandeur, and truth.  His cranium is bald and has only a crown of grey hair remaining.  His emaciated face is full of ardour and power:  his eyes penetrate straight into the splendour of God; and his mouth, although partially hidden by the grey beard that covers the lower part of his face, is praying with extraordinary fervour.  His gesture, so resolute and respectful, is in itself an act of love and charity, and his very hands, so true in drawing and so bold in action, have their special eloquence.  It seems impossible that the divine justice will not allow itself to be swayed by such intercession.

St. Barbara is opposite St. Sixtus.  Her body is in left profile, towards the Virgin, while her head, turned over her left shoulder towards the spectator, appears almost in full face.  Only her left arm and hand are visible, pressed against her breast.  Her left knee, directly resting upon the cloud, sustains the weight of her body; her right leg, which is raised, only touches the clouds with the foot.  Her head is as beautiful, youthful, and fresh as the action of her whole figure is easy, elegant, and noble.  Then where did Raphael find this serenity if not in himself?  The saint, gently bending towards the earth, seems to want to receive our hopes and vows to bear them to Heaven.  She is one of those virgins who are created in the image of the Virgin par excellence.  Nevertheless, here she affects certain worldly appearances which, beside the severe simplicity of the Mother of the Word, establish a hierarchy between the two figures and a sort of line of demarcation that cannot be crossed.  The higher we soar the more is grandeur simplified in everything.