During the 18-year pontificate of Zephyrinus, the young Church endured persecution under the Emperor Septimius Severus until his death in the year 211.

[3] Eusebius insists that Zephyrinus fought vigorously against the blasphemies of the two Theodotuses, who in response treated him with contempt, but later called him the greatest defender of the divinity of Christ.

[1] Zephyrinus's predecessor, Pope Victor I, had excommunicated Theodotus the Tanner for reviving a heresy that Christ became God only after the Resurrection.

Natalius, who was tortured for his faith during the persecution, was persuaded by Asclepiodotus to become a bishop in their sect in exchange for a monthly stipend of 150 denarii.

According to an anonymous work entitled The Little Labyrinth quoted by Eusebius, Natalius was whipped a whole night by an angel, and the next day, he donned sackcloth and ashes and weeping bitterly threw himself at the feet of Zephyrinus.