Louis de Lorraine known as the Cardinal de Guise was the third son of Henry I, Duke of Guise and Catherine of Cleves.

Henry I, Prince of Joinville, Duke of Guise, Count of Eu, sometimes called Le Balafré ('Scarface'), was the eldest son of Francis, Duke of Guise, and Anna d'Este. His maternal grandparents were Ercole II d'Este, Duke of Ferrara, and Renée of France. Through his maternal grandfather, he was a descendant of Lucrezia Borgia and Pope Alexander VI.