Milan, della Rovere, the Colonna and the Orsini have all allied with France. Venice, Spain, and the Holy Roman Empire remain uncommitted.

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.