Henry II de Lorraine, 5th Duke of Guise (Paris, 4 April 1614 – 2 June 1664, Paris) was the second son of Charles, Duke of Guise and Henriette Catherine de Joyeuse.
At the age of fifteen, he became archbishop of Rheims, but the death of his eldest brother Francis in 1639 placed him in the dukedom the following year. He opposed Richelieu, and conspired with the count of Soissons, fighting in the Battle of La Marfée in 1641. For this, he was condemned to death, but fled to Flanders in 1641. His property was seized by the king in 1641, for crime of lèse majesté. Reprieved, he returned in 1643 and his confiscated property was returned to him.
Hoping to make good his family's ancient pretensions to the Kingdom of Naples, he joined the revolt of Masaniello in 1647. The "Royal Republic of Naples" was declared, appealing to the protection of France and nominally headed by Guise (entitled doge in imitation of Venice). However, the tactless Guise rapidly alienated the Neapolitans, and wielded little influence with Cardinal Mazarin. He was captured by the Spaniards in 1648 when the republic fell, and held by them until 1652. He made a second attack on Naples in 1654, but it ended in failure, partly because of the presence of an English fleet under Robert Blake in support of the Spanish.
Afterwards, he settled in Paris, becoming Grand Chamberlain of France to Louis XIV and going deeply into debt because of his expenditures for horses and entertainments. He was the patron of Pierre Corneille, to whom he gave a lodging in the Hôtel de Guise.