Isabella of Spain or Isabel of Spain may refer to:
- Isabella I of Castile (1451–1504), queen
- Isabella II of Spain (1830–1904), queen
- Isabella of Austria (1501–1526)
- Infanta Isabella Clara Eugenia of Spain (1566–1633), archduchess of the Netherlands
- María Isabella of Spain (1789–1848)
- Isabella, Princess of Asturias (1851–1931)