The Plague of Cyprian is a pandemic that afflicts the Roman Empire from about CE 249 to 262.

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.

Its modern name commemorates St. Cyprian, bishop of Carthage, an early Christian writer who witnesses and describes the plague.

The agent of the plague is highly speculative due to sparse sourcing, but suspects include smallpox, pandemic influenza and viral hemorrhagic fever (filoviruses) like the Ebola virus.