[3] The plague is thought to have caused widespread manpower shortages for food production and the Roman army, severely weakening the empire during the Crisis of the Third Century.

[2] The agent of the plague is highly speculative due to sparse sourcing, but suspects have included smallpox, measles, and viral hemorrhagic fever (filoviruses) like the Ebola virus.

But when both we and they had been allowed a tiny breathing-space, out of the blue came this disease, a thing more terrifying to them than any terror, more frightful than any disaster whatever...[8]Cyprian's biographer, Pontius of Carthage, wrote of the plague at Carthage: Afterwards there broke out a dreadful plague, and excessive destruction of a hateful disease invaded every house in succession of the trembling populace, carrying off day by day with abrupt attack numberless people, every one from his own house.

All were shuddering, fleeing, shunning the contagion, impiously exposing their own friends, as if with the exclusion of the person who was sure to die of the plague, one could exclude death itself also.

Fifty years later, a North African convert to Christianity, Arnobius, defended his new religion from pagan allegations that neglect of the traditional gods had resulted in plague and other disasters: [...] that a plague was brought upon the earth after the Christian religion came into the world, and after it revealed the mysteries of hidden truth?

But pestilences, say my opponents, and droughts, wars, famines, locusts, mice, and hailstones, and other hurtful things, by which the property of men is assailed, the gods bring upon us, incensed as they are by your wrong-doings and by your transgressions.

One of the first appearances of this disease relies on the contents of two letters by Bishop Dionysius of Alexandria, pointing to the plague erupting around Easter of 249 AD in Egypt, quickly spreading across Europe, and reaching Rome by the second half of 251 at the latest.

[15] Archaeologists that worked in Thebes, Egypt, uncovered charred human remains leading them to believe that people were burning bodies during the plague.

Cyprian drew moralizing analogies in his sermons to the Christian community and drew a word picture of the plague's symptoms in his essay: This trial, that now the bowels, relaxed into a constant flux, discharge the bodily strength; that a fire originated in the marrow ferments into wounds of the fauces; that the intestines are shaken with a continual vomiting; that the eyes are on fire with the injected blood; that in some cases the feet or some parts of the limbs are taken off by the contagion of diseased putrefaction; that from the weakness arising by the maiming and loss of the body, either the gait is enfeebled, or the hearing is obstructed, or the sight darkened;—is profitable as a proof of faith.

[21] According to the historian Kyle Harper, the symptoms attributed by ancient sources to the Plague of Cyprian better match a viral disease causing a hemorrhagic fever, such as Ebola, rather than smallpox.

The devastation within Rome was so intense that as it overcame the populations, the emperor Trebonianus Gallus and his son gained popularity and support just for providing proper burials spaces for the plague victims, especially the poor and vulnerable.

Cyprian wrote of the passion of the faithful who had fallen ill in his treatise: What a grandeur of spirit it is to struggle with all the powers of an unshaken mind against so many onsets of devastation and death!