In the booksEdit
The Great Spring Sickness was a plague epidemic that followed the Great Spring of 209AL, killing tens of thousands in the Seven Kingdoms. A strong man could wake up healthy in the morning and die by the evening. It killed tens of thousands, especially in the major cities; it was bad in Lannisport, worse in Oldtown, but worst of all in King's Landing, where four in ten succumbed to it.
King Daeron the Good, his last Hand of the King, and his two most immediate heirs, Princes Valarr and Matarys, as well as the High Septon, a third of the Most Devout, and nearly all of the Silent Sisters (who handle the dead) in King's Landing perished to the plague. Lord Brynden Rivers, the Hand of the King to Daeron's successor, Aerys I Targaryen, ordered the many bodies be brought to the Dragonpit and burned by pyromancers. The light of their wildfire pyres could be seen as a glow throughout the city during the night.
The only regions not affected by the plague were the Vale of Arryn and Dorne. The Arryns closed off the Eastern Road at the Bloody Gate to all travel, as well as blocking all travel by sea, isolating the Vale from the epidemic. Similarly, the deserts of Dorne and the narrow passes of the Red Mountains helped to isolate it from the disease's spread.
In terms of its impact, the Great Spring Sickness is loosely Westeros's equivalent of the real-life Black Death, which killed off over a third of the population of Late Medieval Europe.