Pop Skull depicts the lonely and disjointed life of Daniel, a young Alabama pill addict, as his efforts to cope with the trials of his day-to-day life collide with the increasing influence of murderous and displaced spirits that inhabit his home.
Screenwriter E.L. Katz directed the fake vampire film within a film "Evil Whispers". Director Adam Wingard has an appearance in it as the vampire hunter "Raymond".
The scene where the characters of Jeff, Morgan and Daniel go fishing was filmed 14 hours before Hurricane Katrina hit. Cast had to wrap up and leave because the locations were in South Alabama; dangerously close to the coast.