The plague of Justinian or Justinianic plague (541–549 CE) was the first major outbreak of the first plague pandemic, the first Old World pandemic of plague, the contagious disease caused by the bacterium Yersinia pestis. The disease afflicted the entire Mediterranean Basin, Europe, and the Near East, severely affecting the Sasanian Empire and the Byzantine Empire and especially its capital, Constantinople.

The plague is named for the Byzantine Emperor Justinian I (r. 527–565) who, according to his court historian Procopius, contracted the disease and recovered in 542, at the height of the epidemic which killed about a fifth of the population in the imperial capital. The contagion arrived in Roman Egypt in 541, spread around the Mediterranean Sea until 544, and persisted in Northern Europe and the Arabian Peninsula, until 549.