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.

When a group of escaped convicts come across and old looking inn they decide to hide out there. But the guests at this inn get a new kind of room service when a mysterious potion summons a demon and causes a bloodthirsty zombies to rise from their graves in search of live prey.