Empress Irene appointed Elpidius as governor (strategos) of the theme of Sicily. Soon after, however, on 15 April, Irene was informed that he had supported a plot, discovered in October of the previous year to depose her and elevate the Caesar Nikephoros, the eldest surviving son of Constantine V, to power. Irene immediately dispatched the spatharios Theophilos to Sicily to bring Elpidius back to Constantinople. Although his wife and children were left behind in Constantinople, Elpidius refused the summons and was supported by the people and the local army. It does not seem that Elpidius declared himself explicitly in revolt against Irene, but the Empress nevertheless had his wife and children publicly whipped and imprisoned in the capital's praetorium.

In autumn of 781 or early 782, Irene dispatched against him a large fleet under a trusted court eunuch, the patrikios Theodore. Elpidius's own military forces were meager, and after several battles he was defeated. Along with his lieutenant, the dux Nikephoros, he gathered what remained of the theme's treasury and fled to North Africa, where the Arab authorities welcomed him.