Sookie Stackhouse, a waitress with telepathic abilities, falls under the spell of a 173-year-old vampire; Sookie's brother finds himself in hot water.

In a society where humans and vampires co-exist, set in the small town of Bon Temps, Louisiana, Sookie Stackhouse is a young woman who may have found a perfect boyfriend. Sookie is clairvoyant and constantly hears people's thoughts so it makes dating a bit difficult since she tries to keep her ability a secret. When 173-year-old vampire Bill Compton walks into the Merlotte's Bar and Grill where she works as a waitress, she realizes that she can't "hear" what he's thinking, thus giving away his origins since she can't hear the thoughts of those whom are technically dead. Vampires "came out of the coffin" two years ago when the Japanese invented Tru Blood, a synthetic blood substitute. Sookie rescues Bill when a couple of lowlife rednecks, the Rattrays, try to steal his blood to sell on the black market, but she may have a price to pay for interfering. Meanwhile, Sookie's older brother, Jason, is a smooth-talking hustler and lothario who works part-time with a construction crew, and who gets arrested after a local woman that he had a one-night stand with is found strangled. Tara Thornton is Sookie's ill-tempered best friend whom finds her bad-boy brother irresistible. Sam Merlotte is the owner of Merlotte's Bar, who keeps his romantic feelings for Sookie to himself. Lafayette Reynolds is Tara's flamboyant gay cousin and the short-order cook at Merlotte's as well as Jason's co-worker at his construction day job who has more to offer than his gourmet foods. Arlene Fowler is a middle-aged divorcée and another of Sookie's friends and co-workers at Merlotte's looking for a new husband to help raise her two children. Andy Bellefleur is the local police detective working with the collaboration of the town sheriff, Bud Dearborn, who thinks the town may have a killer in their midst as they investigate the strangulation case.

Mack and Denise Rattray get their revenge on Sookie but Bill steps in to save her. Subsequently, Sookie's senses begin to undergo a transformation. She later learns that the Rattrays are dead and the police immediately suspect Bill. She also begins to wonder just how far vampires will go when a leading opponent of the Vampire Rights Act is killed in an accident. Bill agrees to visit Sookie and her grandmother and Tara and Jason invite themselves for the evening. Jason Stackhouse gets to see the video of his evening with Maudette Pickens. The police release him but his experience doesn't dissuade him from sleeping with every woman who will have him.

After Sookie identifies the vampire bartender Longshadow responsible for stealing from Fangtasia, Bill steps in to protect her. In doing so however, he breaks a vampire taboo and must now face the consequences from Eric and his clan for killing one of their own. Knowing he will be away, he asks Sam Merlotte to keep an eye on Sookie. Meanwhile, Jason and Amy take their vampire captive, Eddie, to Jason's house and confine him to the basement. They draw his blood and Jason undergoes an odd transformation. With Amy now working at Merlotte's, Jason spends his spare time just talking to Eddie and they develop a rapport. Elsewhere, Tara visits her mother's exorcist, but decides she can't afford the $800 cost for her own exorcism. Sam agrees to lend Tara the money needed, while he also deals with Detective Andy Bellefleur who becomes suspicious about his past. With Bill away, Sookie chooses to spend the night at Bill's house but wakes up the next morning with a naked man on her bed...

A murder outside Merlotte's leaves everyone reeling.

Vampires and humans clean up in the aftermath of the explosion. Eric tricks Sookie into drinking some of his blood, much to Bill's dismay. As a result of the lapse in security, Godric's leadership falls under review but his response surprises everyone, especially Eric, who begs him not to go through with his plan. In Bon Temps, Maryann is out to find Sam Merlotte and complete the ritual sacrifice. She casts a spell on everyone in Sam's bar to get them to look for him. Lafayette and Tara's mother forcibly remove her from Sookie's house. Hoyt and Jessica get used to their situation and Hoyt decides it's time to introduce his true love to his vampire-hating mother.

Russell captures Sookie and orders Lorena to kill Bill, while Tara remains Franklin's prisoner. Will they be able to escape Mississippi before it's too late?

Eric goes before the Authority following the Magister's disappearance. Tara faces her worst demons. Russell shocks the world with a public announcement.

Sookie learns the truth about what she is.

Tired of being an object of vampire affections, Sookie tries to imagine a life without any supernatural creature.

Sookie has been gone, and everyone's lives have changed without her.

Sookie and Tara adjusts to Bon Temps' new realities.

After his encounter with Marnie and the coven, Eric seems to have lost his memory. He knows he's a vampire but does not recall who he is. Sookie takes him home - he doesn't realize that he owns the house - and contacts Pam for help. Tara is concerned when Lafayette disappears. Jason is still being held prisoner by Crystal and her backwoods clan and learns exactly what they have in store for him. Sam Merlotte takes his brother Tommy to task for wanting to cheat Mrs. Fortenberry out of a possible fortune. Jessica seeks Bill's advice after feeding on a pick-up at Fangtasia. Sookie gets a surprise visit from the faerie world.

Eric has disappeared again and Sookie enlists Alcide help in finding him. Bill wants to find him as well. Pam meanwhile wants Marnie to reverse her spell on Eric. She gets more than she bargained for. Bill gets to meet Portia Bellefleur's mother but learns something about her that brings their relationship to an abrupt end. Jason manages to escape from Crystal and her clan and is eventually rescued by familiar faces. Terry and Arlene's baby has a message for him. After his falling out with Sam, Tommy finds his mother but isn't quite expecting the kind of welcome he gets.

With Pam's body now rotting as the result of the witch's spell, Bill decides to take action and imprisons Marnie, who continues to have visions of an ancient spirit. He wants her to reverse the spell she's placed on Pam but she says she simply doesn't know how. Bill is none too pleased when he learns that Sookie is hiding Eric. Neither is Tara who refuses to believe that Eric has changed. Meanwhile, Jason is recovering and has an erotic dream involving Jessica. He also learns that a full moon is in the offing. Arlene and Terry decide they need an exorcism and seek some local help. Lafayette and Jesus head to Mexico to get some help of their own.

Bill is livid when he hears that Sookie has been hiding Eric in her house. He arrests him and puts him in the same cell with Pam, who is still rotting away. He also asks the Authority to put Eric to the true death. Marnie is also in Bill's prison but connects with the spirit of the witch from the past who had a deadly spell for dealing with vampires. It's also a full moon and Jason fully expects to turn into a were-panther. Sookie sits up with him but when he runs off into the woods, it's Jessica who comforts him. With Sam away taking care of Arlene's burnt out house, Tommy shifts into something he has never experienced before. In Mexico. Lafayette and Jesus seek help.

With Marnie empowered by spirits of the dead, Bill issues an unpopular order to save vampires from the light. Eric embraces his amnesia; Luna discovers Sam is not the man she thought he was; Lafayette expands his consciousness; Pam gets a body peel; Andy's date with Holly doesn't go as planned; Jessica has doubts about her future with Hoyt; Alcide and Debbie join a new pack.

As Bill and Marnie brace for a dangerous midnight faceoff, Sookie and Eric pledge their allegiance to the King. Jason is torn between friendship and passion, and Jessica is spurned from two homes; Lafayette becomes the pawn of a tormented spirit; Tommy takes a walk in someone else's shoes; Sam contends with yet another adversary in Marcus, Luna's ex and the leader of Alcide's new pack.

Convalescing after her latest near-death trauma, Sookie envisions a world where there's room for both Bill and Eric. Jesus tries to purge the restless spirit out of Lafayette; Marcus enlists Alcide to help him deal with the Sam situation; Bill and Nan Flanagan clash over their agendas; Hoyt asks Jason to make a delivery to Jessica; despite Tara and Holly's misgivings, Marnie plots her next move against the vampires, during a "Festival of Tolerance" event at Shreveport.

As all hell breaks loose in Shreveport, Sookie summons her most potent powers yet to save Bill, in the process breaking a spell and leading Marnie/Antonia to re-evaluate her mission. Jason urges Jessica to glamour him for Hoyt's sake; Terry drags Andy to "Fort Bellefleur" for an intervention; Alcide reconsiders his allegiances after Marcus fight with Tommy; Jesus, accompanied by Sookie, Lafayette and Jason, tries to breach the Moongoddess Emporium's defenses to liberate Tara and Holly, while Bill leads a brigade of vampires committed to blowing the place to kingdom come.

Bill, Eric, Pam and Jessica descend on the witch's coven, intent on killing Marnie and anyone else who poses a threat to them. They're not quite prepared for the barrier Marnie has set up around the emporium and realize they may have a bigger fight on their hands than they had anticipated. Inside the emporium, Marnie is having her own problems with Antonia, who is no longer as keen as her host to destroy the vampires. Even after the vampires find a way in, it appears that Marnie will not be easily disposed of. Sam and Alcide track down Marcus who has kidnapped his own daughter. Sam wants to end any threat to Luna and her daughter. Andy Bellefleur meanwhile has an interesting encounter in the woods.

Now free, Sookie must decide between Eric and Bill. It's not an easy decision and she soon realizes that her turmoils are not yet over when someone comes gunning for her. Having taken over Lafayette's body, Marnie is intent on seeking revenge. She also wants additional powers however and knows exactly where to get them. Sookie has to save Bill and Eric from her but gets help from an unexpected source. Jason meanwhile decides it's time to tell Hoyt about sleeping with Jessica. Hoyt doesn't take it too well. Jason and Jessica however come to an understanding about their relationship. Andy Bellefleur tries to make amends about his recent strange behavior and Arlene gets a visit from the last person she wanted to see.

Sookie hatches a dangerous plan to take down the H-Vamps; Jason eyes a family future with Violet; Willa is forced to find a new place to stay; Sarah Newlin sheds her past; Pam offers Eric a compelling reason to return to Louisiana.