Thanks to a Japanese scientist’s invention of synthetic blood, vampires have progressed from legendary monsters to fellow citizens overnight. And while humans have supposedly been removed from the menu, many remain apprehensive about these creatures “coming out of the coffin.” Religious leaders and government officials around the world have chosen their sides, but in the small Louisiana town of Bon Temps, the jury is still out.

Local waitress Sookie Stackhouse (Anna Paquin), however, knows how it feels to be an outcast. “Cursed” with the ability to listen in on people’s thoughts, she’s also open-minded about the integration of vampires — particularly when it comes to Bill Compton (Stephen Moyer), a handsome 173-year-old living up the road. But as Sookie is drawn into a series of mysteries surrounding Bill’s arrival in Bon Temps, that tolerance will be put to the test.

The first season’s plot revolves around the murders of young women in the town of Bon Temps. The likeliest suspect is Jason, the brother of Sookie, who has had sexual relations with several of the victims. At first Sookie herself wonders if her brother is guilty, but then thinks he is not, and at the urging of her grandmother, she begins to use her gift to try to solve the mystery. As Sookie attempts this, her grandmother is also murdered. Her boss, Sam acts suspiciously. Her brother has developed an addiction to V-juice (vampire blood) and Bill, her vampire love interest, is also a possible suspect. As Sookie investigates the murder, she wavers between loving Bill the vampire, and her boss Sam. Then she finds out that Sam is a shapeshifter and can turn into a dog.

The murderer turns out to be Rene, a man who works with Jason and frequents the bar at which Sookie waits tables. He has been killing women he suspects of sleeping with vampires, including his own sister. Sookie stumbles on to this information after being driven home by the murderer, and gives herself away. There is a chase during which Sam the shapeshifter attacks Rene in dog form, and Bill the vampire goes out into the daytime to try and save her even though he nearly burns to death. Both of these heroic efforts fail, and Sookie herself kills Rene with a shovel.

The series ends with the arrival of a immature vampire named Jessica, whom Bill sired, coming to live with him against his wishes, and the discovery of a body found in the car of a local detective. Thus far the body is only identified as an African-American with brightly painted toe nails. It is likely, though not necessarily, that of short order cook, Lafayette.

In a separate storyline, Tara, Sookie’s best friend, begins a sexual relationship with Sam, which leads to stronger feelings. Tara is led to believe that she suffers from possible demon contamination; she has been traumatized by her upbringing by an alcoholic mother.

There is a brief encounter with the vampire hierarchy, including the sheriff of area five (which includes Bon Temps), Eric, and his second in command, Pam. In the last two episodes, a wealthy social worker, who travels with a pig, enters the story.