The magnificent Baroque chapel in the left aisle was founded by Pope Paul V Borghese (1605-1621), and is named after him. The edifice was designed by Flaminio Ponzio, who was also responsible for the memorials to Pope Paul and Pope Clement VIII. The chapel was built between the years 1606 and 1611, but the decoration was not completed until the end of 1616. The chapel was consecrated on January 27, 1613. Colored marbles, gulding, and precious stones combine to give an impression of dazzling splendor which surpass the harsher color effects of the Cappella Sistina.

The chapel was built for two functions. Firstly, it became the burial place of the Borghese family. As a result, the family became responsible for the chapel's upkeep for centuries and so the edifice is sometimes called the Cappella Borghese. Secondly, it became the shrine of the venerated icon of Our Lady, Salus Populi Romani and as such has been a focus of popular local devotion to the present day.

The small side chapel to the right as you enter, behind the entrance arch, is dedicated to St. Charles Borromeo. It was built shortly after the canonization of the saint by Pope Paul V on 29 May 1608.

The small side chapel to the left as you enter, behind the entrance arch, is dedicated to Santa Francesca Romana, the patron saint of Rome. It was built shortly after the canonization of the saint by Pope Paul V on 1 November 1610.