In December 1656, only four months after the death of her first spouse, she married her cousin Antonio II Tassi (1623-1672), Marchese di Paullo and captain of the royal guard of the viceroy of Naples.
On 31 January 1659, Giovanna De Grandis was arrested in Rome and imprisoned in the Papal prison at Tor di Nona, which was the beginning of the infamous Spana Prosecution, exposing Gironima Spana's network of poison dealers in Rome.
In April, Spana's maid Francesca Flore was interrogated, and implicated Sulpizia Vitelleschi in her testimony.
The testimony of Francesca Flore appeared to confuse the dates, since in 1657, Sulpizia Vitelleschi had been married to her second spouse, who was still alive, since the year prior.
Out of consideration of the social rank of Sulpizia Vitelleschi, the authorities refrained from considering the possibility that the dates may have been confused and from examining the death of her first spouse, and her name was not mentioned further in the investigation.