In 1527, Felice was not staying in the Orsini Palace at Monte Giordano when the Sack of Rome began, and this likely saved her life, as it was one of the first palaces to be attacked. She and her children were with her mother, Lucrezia, and half-siblings Gian Domenico and Francesca at the De Cupis palace when the Sack began. They decided that it would be safest to divide by gender and flee Rome. The women dressed in plain clothes, hid their jewels underneath their dresses and went to Isabella d'Este's rented castle, Dodici Apostoli, which provided refuge to 1200 noblewomen and 1000 noblemen and was one of the only palaces not attacked because Isabella's son was a chief lieutenant leading the attack. The palace was soon put under ransom. Felice paid for herself and a few others, including 2000 ducats for her nephew Cristofano. Felice and her family then fled Rome for Ostia where they took a boat to Civitavecchia and were united with the rest of Felice's family. The family split up again because Felice wanted to be far from Rome to protect her children from Napoleone, who was stationed at Felice's Bracciano estate with some followers. Felice feared that Napoleone might use the chaos of the sack as an opportunity to kill his half-siblings and reclaim what he believed to be his rightful inheritance of the Orsini lordship. Felice and her children went to stay with her cousins in the Duchy of Urbino, where she received a palace in the hillside town of Fossombrone. In Fossombrone, Felice helped noblemen and women in Rome, sending money and coordinating supplies.