Catherine de Clèves (or de Nevers) (1548 – 11 May 1633) was the wife of Henry, Duke of Guise, and matriarch of the numerous and influential House of Guise. By marriage she was Duchess of Guise from 1570 to 1588, and Dowager Duchess of Guise thereafter. She was Countess of Eu in her own right from 1564.

Catherine was the second daughter of François de Clèves, Duke of Nevers, and Marguerite de Bourbon, elder sister of Antoine de Bourbon.

She was the first cousin of Henry of Navarre, sister-in-law of Henri de Bourbon, Prince of Condé, and great aunt of Ludwika Maria Gonzaga, Queen of Poland.

At the age of twelve, Catherine married Antoine de Croÿ, Prince de Porcien (or Porcean), who died seven years later. After the conventional three years of mourning, on 4 October 1570, she married Henri de Lorraine, Duke of Guise, who was two years her junior.

They had fourteen children, including Charles, Duke of Guise and Louis III, Cardinal of Guise. She had a widely publicised affair with a young nobleman, Saint-Mégrin, who was killed by her husband. The event is dramatised in the Alexandre Dumas play Henri III et sa cour (1829).

Henry of Guise was the leader of the fervently Catholic faction in the French Wars of Religion. From 1584, the conflict among factions led by Henry of Guise, Henry of Navarre, and Henry III of France was known as the War of the Three Henrys. In 1588, Henry of Guise was assassinated on the orders of King Henry III.

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