|Dislikes:||Double, The Medici Mafia|
|Voiced by:||Erin Fitzgerald|
Selene and her family were once in a close relationship with the Medici until Double tricked her into obtaining the Skull Heart. Soon the Medici Mafia found out about her ownership of the heart and proceeded to assassinate her family in order to seize the Skull Heart for themselves. It is unknown how many people were killed during this event, though it is shown that Squigly was at least a victim in the attack. Selene, in a sense of desperation at the loss of her family, wished for her slaughtered family to return back to her, unintentionally transforming her into the next Skullgirl. Under the influence of the Skull Heart, she killed her husband, Roberto, who had warned Leviathan to "Stop anybody who gets close - even me!" before the Parasite made Squigly his new host. Her wish was granted when her family was reanimated as undead and commanded the undead legion as the Skullgirl.
14 years after Selene had become the Skullgirl, Squigly reawakens from the dead with the emergence of Marie. After successfully defeating Marie, she discovers that it was Double in disguise who had tricked Selene in a bid to foil their relationship with the Medici Mafia - a deed in which she had succeeded in.
- Selene's name is pronounced "seh-leh-nay."