Finally released from prison, Elwood Blues is once again enlisted by Sister Mary Stigmata in her latest crusade to raise funds for a children's hospital. Hitting the road to re-unite the band and win the big prize at the New Orleans Battle of the Bands, Elwood is pursued cross-country by the cops.

Devastated by his girlfriend's sudden death, Joey tries to keep her spirit alive by carting her corpse along with him on an interstate road trip. But when his lover's body begins to decompose, Joey's morbid journey only serves to make his loss more painful.