Philip II, King of Spain (b. 1527) married a) Maria Manuela of Portugal (b. 1527-1545) in 1543, b) Mary, Queen of England (1516-1560) in 1554, c) Anna of Austria (b. 1549) in 1565
- a) Charles, Prince of Asturias and Girona (1545-1568) married Elisabeth of France (1545-1568) in 1559 with issue
- Philip (1561)
- stillborn twin girls (1564)
- Isabella II, Queen of Spain (b. 1566) married Ferdinand VI, King of Spain (b. 1566)
- Charles I, King of Portugal (1567-1572)
- Catherine (1568)
- b) Katherine Isabella, Queen of England and Duchess of Burgundy (b. 1555) married Ernest I, King of England (b. 1553) with issue
- c) Ferdinand VI, King of Spain (b. 1566) married Isabella II, Queen of Spain (b. 1566)
- c) Juana Manuela (1568-1574)
- c) Leonora Maria (b. 1570)
- c) Isabella Clara Eugenia (1572-1575)
- c) Diego (b. 1575)