Isabella of Portugal (Portuguese: Isabel; October 24, 1503 – May 1, 1539) is an Infanta of Portugal, by birth, and a Holy Roman Empress, Queen of Germany, Italy, Spain, Naples and Sicily, Duchess of Burgundy etc.

as the spouse of Charles V, Holy Roman Emperor.

She is the daughter of Manuel I of Portugal and Maria of Aragon.

She serves as regent of Spain during the absence of her spouse for long periods.