Sixtus II was pope from August 30, 257 to August 6, 258, following Stephen I as bishop of Rome in 257. He died as a martyr during the persecution by Emperor Valerian.

According to the Liber Pontificalis, he was Greek by birth. He restored the relations with the African and Eastern churches which had been broken off by his predecessor on the question of heretical baptism.

In the persecutions under Emperor Valerian I in 258, numerous priests and bishops were put to death. Pope Sixtus II was one of the first victims of this persecution, being crucified on August 6.

He is thought to be the author of the pseudo-Cyprianic writing Ad Novatianum, though this view has not found general acceptance. Another composition written at Rome, between 253 and 258, is generally agreed to be his.