Isernia is a town and comune in the southern Italian region of Molise, 41°46N, 14°14E at 423 m (1388 ft) above sea level. It is the capital of Isernia province. The commune has a surface of 68.74 sq. km, and a 2003 population of 21.300.

Situated on a rocky crest rising from 350 mt to 475 between the Carpino and the Sorsi rivers, Isernia still reflects with its road plan the ancient structure of the Roman town, with a central wide street and side streets on both sides. It is now the Capital city of the province of Isernia, and a flourishing center of pasta makers, stone work, embroidery crafts. The name of the town come from the italic root "aiser" meaning "god".

With the name of Aesernia was the capital of the Samnites, and in 263 Rome established a colony here, a key communication center between Southern Italy and the inner Appennine Regions. During the Social Wars against Rome, the Italic League established here their capital after abandoning their previous capital Corfinio . It was a Roman "municipium" and its inhabitants enjoyed Roman citizenship. In 800 it was destroyed by the Saracens, then sacked in 1199 by Marcovaldo, Count of Molise, then set on fire in 1223 by the soldiers of Frederick II. In 1519 it was freed from the feudal servitude by king Charles V and became a free city. Massive destruction was caused by earthquakes in 847, 1349, 1456 and 1805. During the Second World War, in September 1943 Allied air bombings destroyed over half city, killing one third of the population.

Its patron saint is San Pietro Celestino , born Pietro Angelieri in the vicinity of Isernia, whose feast is on 19 May.