A resident at the court of her cousin, Honorius, she selected a bride for the court poet, Claudian, and took care of Honorius' half-sister, her cousin Galla Placidia. She and Stilicho had a son, Eucherius, and two daughters, Maria and Thermantia, both of whom married Honorius.
According to the pagan historian Zosimus, Serena took a necklace from a statue of Rhea Silvia and placed it on her own neck. An old woman, the last of the Vestal Virgins, appeared, who rebuked Serena and called down punishment upon her for her act of impiety. Serena was then subject to dreadful dreams predicting her own untimely death.
Stilicho was executed on Honorius' orders in 408. During the siege of Rome by the Visigoths the following year, Serena was falsely accused of conspiring with the Goths, and was executed with Galla Placidia's consent.