After hearing about this defeat, Manuel and his father fled to Coimbra to avoid imprisonment, and gathered six thousand men to face the Spanish troops once again.

With no options left, Manuel and his father were forced to hide in monasteries and friends' houses until they fled to France with the rest of the family.

Before, António went to England, asking for Queen Elizabeth I's support, which was granted, but the English troops never arrived to Portugal due to a bout of plague that killed most of the soldiers.

On 7 November 1597, Manuel wed Countess Emilia of Nassau (1569–1629), a daughter of William I, Prince of Orange and Princess Anna of Saxony.

Their families opposed the marriage but this did not prevent the couple from being secretly married by a Roman Catholic priest.

Therefore, he started secret negotiations with the stewards of the Catholic Spanish Netherlands, the infanta Isabella Clara Eugenia and her husband Albert VII, Archduke of Austria, who promised them a higher apanage than House Orange was paying.