As Giulia gives birth, Rodrigo and the remaining Cardinals discuss the state of war. Della Rovere is poised to take over as pope. Switching strategies, Rodrigo gives Charles permission to pass through Rome.

At the French encampment, Djem learns of his son's murder by his brother, Bajazet. Distraught, he falls ill. Cesare uses the opportunity to escape and informs Lucrezia that d'Este is in a hospital in Rome. Lucrezia goes to visit him, where she learns that he is suffering from the "French Disease." Heartbroken that he has been with other women, she asks Rodrigo for permission to join the convent.

Having learned that his wife died in childbirth, an angry Juan confronts Lucrezia about her role in Maria Enriques' escape. Lucrezia is devastated, firm in her resolve to remain a nun she visits Lucia to ask how she may be "blessed" with stigmata. Cardinal Carafa reveals the people of Naples have chosen Federigo d'Aragona to be their king.