Fluffy belonged to Samantha Maxis, the daughter of Ludvig Maxis, and was first mentioned in Der Riese by two of the radio messages. One radio broadcast hears Dr. Maxis giving Fluffy to Samantha. He tells her that she is pregnant and is expecting puppies soon. Samantha asks if she can keep the puppies too. Dr. Maxis says that they'll see, and that it will be taken "one step at a time." The plan seems to fall to pieces soon afterwards, as Fluffy is secretly experimented on by Edward Richtofen and Maxis (unknown to Samantha). The experiment was to try and teleport an animal instead of a human, but the experiment was ruined when Samantha walked in on both Maxis and Richtofen preparing Fluffy for the teleportation test. After teleporting Fluffy with Samantha still in the room, Edward Richtofen then enacts his plan of revenge, locking both Samantha and her Father inside, with Fluffy, who has turned into a Hellhound after the teleportation. Richtofen then turns the teleporter on with Maxis and Samantha inside, potentially killing them.
Because Fluffy was pregnant with puppies, she gave birth to living Hellhounds. Shortly following this, the Der Riese facility was overrun by Zombies and Hellhounds.
In the end cutscene of Origins, Fluffy is seen alongside Samantha and Eddie.
Fluffy also appears in the intro cutscene of the map The Giant in which she is already zombified with Samantha and Ludvig Maxis trapped in the teleporter.