Sookie is 25 years old and works as a barmaid at Merlotte's. She lives in Bon Temps with her grandmother, Adele. She also has an older brother, Jason, but he lives on his own. Her parents died in a flash flood when she was young.
Since her childhood, Sookie has been capable of reading people's minds, but she doesn't see it as a blessing. Because of her "disability", she can't help knowing what other people are thinking all the time, unless she concentrates and "puts up her guard". That's why she never wanted to go to college, because she wouldn't have been able to study and repress her gift at the same time. Furthermore, she never had a boyfriend or sexual relationships because she couldn't feel comfortable if her partner thought something bad about her.
Early in the book, Sookie meets a vampire, a Civil War veteran named Bill Compton, while working at Merlotte's. After first meeting Bill, Sookie saves him from the Rattrays, a couple of drainers (people who steal blood from vampires). Then, Sookie realizes she cannot read the minds of vampires. Bill returns the favor several days later when the Rattrays attack Sookie, in revenge. Sookie ends up seriously wounded, but Bill gives her his blood, so she can heal quickly.
In the following days, Sookie tells her Gran about Bill (except the Rattray's revenge part), and Gran seems interested in him, too. She asks Sookie to invite Bill to the club of Descendants of the Glorious Dead, which Adele often attends, so that Bill can talk about the Civil War from a real point of view. Bill is then invited to Gran's house and, after meeting her, he and Sookie go out for a walk. During the walk, Bill tells Sookie about being a vampire, and Sookie tells him about being a telepath. Also, Sookie learns she can't be glamered by a vampire. When Bills takes her home, they share their first kiss.
Sookie starts to feel something for Bill, so she drops by his house on the pretense of hiring a plumber for Bill. But he is with another three vampires, wilder and crueler, and a couple of humans. Vampires Malcolm, Diane, and Liam aim to feed on Sookie, but Bill defends her, claiming "she is mine". Then, Sookie discovers one of the humans is allowing the vampires to feed on him because he has a virus that debilitates them. She tells them, and the trio leaves with the fang-bangers, but Sookie becomes terrified by how evil some vampires can be. She takes time apart from Bill.
The next day, Sam, Sookie's boss, asks her to drop by Dawn's house, another barmaid of Merlotte's, because Dawn hadn't show up in a few days. Sookie does this favour for Sam and finds Dawn dead, strangled and bitten by a vampire. The murder looks like another recent one, that of Maudette Pickens. It seems like a serial killer is on the loose. Sookie decides to investigate on her own. She asks Bill to take her to a vampire bar, Fangtasia, in the neighboring town of Shreveport.
They get there and ask some questions about the victims. They confirm both liked being bitten by and having sex with vampires, but not much more. However, Sookie meets Eric Northman, the owner, a vampire sheriff much older and more powerful than anyone in the club. She also meets his progeny, Pam, a female vampire. Eric is drawn to Sookie and tries to glamer her. Also, Sookie reveals she is a telepath to Eric.
The day the meeting of Descendants of the Glorious Dead is going to be celebrated, Sam invites Sookie to go together, as kind of a date. Sookie, without knowing why, accepts. Bill charms the audience and seems jealous of Sam. After dinner, Sam takes Sookie back home and kisses her, but she doesn't kiss him back. When Sookie enters her house, she discovers Gran dead on the kitchen floor. Bill soothes her. After the funeral, they make love for the first time.
As their relationship deepens, Sookie tells Bill she was molested by her uncle Bartlett while growing up. Bill kills him, and Sookie asks Bill for time to consider whether or not they would be able to have a normal life together. They come back together after a mob burns down the house of Malcolm, Diane, and Liam for misbehaving in town. Sookie thinks at first that they could have killed Bill too, as they were "friends", but Bill hides out, burying himself in the soil in the cemetery between Sookie and Bill's houses.
At some point, Eric commands Bill to direct Sookie to use her ability to determine the identity of whoever is embezzling funds from Fangtasia. Bill, fearing this is a trap, gives his blood to Sookie, to make her stronger. Sookie agrees to read a few minds, but insists Eric agrees to give the culprit to the police, not torture or kill them. In exchange, she agrees to work for Eric anytime. For a moment, Sookie hears Eric's thoughts, which are he wants to mainstream and keep legal. Sookie discovers the thief is Long Shadow, Eric's partner and a vampire. A confrontation ensues that nearly kills Sookie. Eric saves Sookie's life by staking Long Shadow when he attacks her. He makes clear he fancies Sookie and wants her to be his, no matter what the cost.
Bill, concerned with Eric's power over him and Sookie, decides to improve his own position within the vampire hierarchy. He asks Bubba, a dim-witted vampire who was "the man from Memphis", to protect Sookie while he is gone. One night, Sookie receives a strange call from Merlotte's, and she goes there to meet her brother Jason, but finds out he hasn't been there all night. On her way back home, she finds an abandoned dog and takes him home with her. Next morning, Sookie discovers her boss is a shape-shifter, when she finds a naked Sam instead of the dog she adopted.
Her brother Jason is arrested for the murders of Maudette Pickens and Dawn Green, as the police find recordings of him and the victims having rough sex. Sookie pays the bail and tries even harder to discover who the killer is.
Despite being guarded by Bubba, Sookie is attacked one night by her brother's friend Rene Lenier. He almost kills her, but she fights back, thanks to Bill's blood. Badly injured, Sookie awakens in the hospital and finds the police by her side, telling her Rene has confessed to the killings. Bill appears later that night and tells Sookie that he has become his area's investigator, working under Eric, so he can better protect both himself and Sookie from Eric.