The Plague of Cyprian ravaged the Roman Empire for about four years (or fifteen assuming that the references to disease refer to the same thing) in the middle of the third century. Our information on this event is changing rapidly, but currently it looks like the cause was some sort of filovirus such as Ebola. It’s been credited with helping to usher in the rise of Christianity as well as the Crisis of the Third Century

SOURCES
The Fate of Rome, Harper
The Plague of Cyprian, Huebner
The Roman Empire from Severus to Constantine, Southern
The Late Roman Army, Southern
The Fall of Rome: The Military Explanation
Imperial Rome AD 193 to 284, Ando