Lenore was part of a group of vampires who had sworn off consuming human blood, and instead fed on the blood of cows. She explained to Sam that while she found cow blood disgusting, it was worth being able to live in peace and not draw attention from hunters.
Despite her efforts, though, she and her nest were hunted by an obsessed vampire hunter named Gordon Walker, whom Sam and Dean had just met while investigating a case. Her group kidnapped Sam from his motel room and brought him to their nest. There, Lenore asked Sam to help the vampires escape and stop Walker from killing them.
When Sam was released, he returned to his motel room and pleaded the vampires' case to his brother. Gordon overheard him and went after Lenore's nest on his own. Once the Winchesters realized Gordon overheard them and left to kill them himself, they went to the nest. There, Gordon had Lenore tied up and had been torturing her with a knife dipped in dead man's blood.
When the boys arrived, they attempted to talk Gordon out of killing Lenore, but Gordon argued that all vampires were bloodthirsty killers, even Lenore and her nest. To prove his point, Gordon grabbed Sam's arm and cut it with his knife, and held his arm above Lenore's face. When his blood dripped onto her, Lenore's vampire instincts kicked in and she moved towards the blood. However, after a moment, she was able to overcome it, and reverted to normal. With their point proven, Sam escorted Lenore out and helped her leave town.
While Sam, Dean, Bobby and Castiel are searching for Eve, they require a "good monster", one who can give them inside details on Eve. Castiel brings Lenore and at first she attempts to run but is cornered. She brings up when Gorden Walker tried to kill her and Sam reveals his eventual fate of being decapitated. Sam asks her for Eve's location, but Lenore wants nothing to do with Eve and is still trying to escape her. Sam also asks about her nest and she tells them they could no longer resist Eve's voice and began killing again, due to Eve's voice in their heads and what it does to them. She was forced to hide in a basement and expresses the lust of feeding she battled, remarking that "everyone gives in".
Dean asks again for the location of Eve and Lenore tells them that if she does reveal to them the location, Eve will know they are coming. They still insist, so Lenore finally reveals that Eve is in Grants Pass, Oregon. In return, she asks the brothers to kill her, due to her shame in having relapsed and having fed on a human recently. Sam and Dean are reluctant, but Castiel steps in and smites her.
- She is the first recurring vampire.
- She is, to date, the only known female pack leader; all the other vampire leaders who have been introduced have been men, and unlike Celia who is a "mother" to a family of vampires.
- Her actress, Amber Benson, is best known for portraying the witch Tara Maclay in Buffy the Vampire Slayer, which also starred fellow Supernatural guest starts Mercedes McNab, James Marsters, Charisma Carpenter, Harry Groener and Felicia Day.