To the right of the high altar is the enormous domed Blessed Sacrament Chapel, also called the Cappella Sistina after its founder, Pope Sixtus V. The pope had actually begun work in 1584, the year before his election when he was still Cardinal Felice Peretti. The architect was Domenico Fontana, who used some of the polychrome marble spolia available from the demolition of the ancient Septizodium. Work continued on the edifice until 1587, and on its decoration and monuments until 1590.

The small side chapel to the left as you enter, behind the entrance arch, is dedicated to St. Jerome.

The little domed octagonal chapel to the right just inside the entrance gate is dedicated jointly to St Lucy and the Holy Innocents.