Jody, a young single red-headed woman living in San Francisco, is attacked by a vampire and soon realizes that she has become one herself. While trying to adjust to her new nocturnal lifestyle, she is aided by C. Thomas Flood ("Tommy"), a wannabe writer who just moved to town and works nights at a local supermarket. As Jody and Tommy begin their life together (and become attracted to each other), they also discover that a recent string of mysterious murders may be linked to the vampire who attacked Jody. To get to the bottom of the matter, they engage the help of Tommy's friends at work and a mysterious street person named "The Emperor"
Despite the gruesomeness of the general story, there is a certain vampiric benevolence here in that Jody survives by preying upon people who are already very near death themselves (e.g., AIDS sufferers, etc.). This principle plays into her cameo appearance in the author's later novel A Dirty Job.
A sequel to Bloodsucking Fiends, entitled You Suck: A Love Story, was published on January 16, 2007.