Vittoria della Rovere
She gave her husband four children, two of which would survive infancy the future Cosimo III and Francesco Maria de' Medici, Duke of Rovere and Montefeltro. She was the Duchess of Rovere and Montefeltro in her own right and these went to her youngest son when she died. She was later the guardian of her three grandchildren. Her marriage bought a lot of art treasures to the House of Medici which are today at the Palazzo Pitti Uffizi Gallery in Florence. She did not get on with her daughter in law Marguerite Louise d'Orléans.
- Cosimo de' Medici, Grand Prince of Tuscany (19 December 1639 - 21 December 1639) died in infancy.
- Unnamed son (1640)
- Cosimo III de' Medici, Grand Duke of Tuscany (14 August 1642 – 31 October 1723) married Marguerite Louise d'Orléans and had issue.
- Francesco Maria de' Medici (12 November 1660 – 3 February 1711) married Eleonora Luisa Gonzaga, no issue.