The Tarellian plague was a deadly disease that struck the Tarellian race at an unknown date. Its existence dates back to at least the 22nd century where it is jokingly mentioned by Dr. Phlox in regards to Ensign Mayweather's headache (ENT: "Singularity"). By the early 2360s, the plague had all but wiped out the species.

In 2364, a Tarellian plague ship approached the planet Haven, as its crew believed the planet contained a cure for the plague. The group was successfully turned away from settling on Haven after meeting the USS Enterprise-D in orbit. During the encounter, Dr. Wyatt Miller beamed over to the plague ship with medical supplies from the Enterprise, believing it was his purpose to find a cure for the plague. (TNG: "Haven")