Dom João Manuel, Hereditary Prince of Portugal (Portuguese pronunciation: [ʒuˈɐ̃w mɐnuˈɛl]) (3 June 1537 – 2 January 1554) was a Portuguese infante (prince), the eighth child of King John III of Portugal by his wife Catherine of Austria, daughter of Philip I of Castile and Joanna of Castile.

João Manuel was born on 3 June 1537 in the Royal Palace of Évora and became the heir to the throne of Portugal in 1539.

He survived his four older brothers who died in childhood but was a sickly teenager.

The successive inter-marriages between the houses of Spain and Portugal are believed to have some responsibility for his ill health.

On 11 January 1552, he married Princess Joanna of Spain, his double-first cousin, through both paternal and maternal line, daughter of his paternal aunt Isabella of Portugal and of his maternal uncle, Emperor Charles V. João Manuel died of what the sources refer to as consumption, the old term used to refer to tuberculosis, on 2 January 1554, but some historians believe his death occurred as a result of diabetes, a disease inherited from his maternal grandfather, Philip I. Eighteen days later, a posthumous son was born, who later became Sebastian I of Portugal.