In their three years of marriage, they had two children, a son who died in infancy and a daughter, Elisabeth, future Queen of Spain.

On 7 December 1696, Dorothea married Odoardo's half-brother, Francesco Farnese, who had become Duke of Parma when his father died in 1694.

The previous day, he had announced that his wife, Enrichetta d'Este, was pregnant; after his death, a regency council for the potential heir was formed, consisting of Enrichetta, a bishop, the first secretary of state and two gentlemen of the court.

[5] Queen Elisabeth in Spain convinced her mother to have Enrichetta examined again on 13 September 1731; it was then reported that there was in fact no child, and the House of Farnese was extinct.

Dorothea ruled as regent until 1735, when the duchy was ceded to Austria after the War of the Polish Succession.