Minding his own business on his shift for the Portland Parks and Recreation department, Ryan Gilko gets violently rear-ended by a driver with some serious road rage. Gilko gets out of the car to talk to the driver behind him and discovers him pockmarked and appearing to be very ill. The man is completely disoriented and violent, almost zombie-like; Gilko retaliates, pricking him with his quills as he morphs into a Stangebar, a porcupine-like Wesen. The driver recoils, and then staggers into a nearby building where he passes out from illness. A traumatized Gilko calls 911, and then Nick and Hank arrive on the scene.
After hearing the story breakdown, Nick and Hank cautiously approach the empty office building where the attacker is. They discover a trashed office space and a completely disoriented and destructive attacker. Stanton glowers and morphs into a Renigen before he comes after Hank and Nick. Left with no other choice, Hank and Nick both fire their guns until Stanton collapses dead on the floor. Nick tells Hank that this is an abnormal incident... even for the Wesen world.
Meanwhile, Juliette struggles to put back the pieces of her relationship with Nick. She calls Monroe and even has coffee with Bud, trying to remember anything at all about their time together. When Nick arrives home, Juliette tells him how awful she feels - like she's done something wrong but doesn't know how to fix it.
On the phone with his cousin, Renard gets word of a Nucklavee (a terrifying horse-like creature) coming to Portland to come after Nick. Renard won't have it and prepares for this next creature's arrival. He even gets the police involved, saying that there's a fugitive coming to Portland that they need to prepare for.
Gilko hardly emerged unscathed from his run-in with Stanton. A rash starts developing, and he sees himself turning sickly and erratic. As much as he resists, there's no denying it: Gilko has contracted this horrible Wesen plague. And things are only getting more dangerous by the minute.
Somehow, Monroe and Rosalee manage to find romance in the midst of this madness. Monroe uncovers his great grandma's picnic basket and comments to Rosalee that he hasn't been on a picnic in ages. The two embark on an adorable date into the woods, and things start to get cozy. Both comment that they've rushed things in the past and want to take it slow. And just when they're about to kiss, an interruption comes from the forest; someone is there! Gilko moving towards them, in the throes of the advancing disease. And he scrapes Rosalee before they get a chance to make a run for it.
Meanwhile, Nick goes to his aunt's trailer to investigate this horrifying Wesen disease. He discovers that it is Fluvus Pestilentia, also called the Yellow Plague. The book shows illustrations of piles of dead bodies; apparently the disease ravaged the Wesen world long ago. If the Yellow Plague is back, it can only mean terrible things.
After making their escape from a diseased Gilko, Monroe and Rosalee return to the shop. They think they've escaped a terrible attack, but assume so too soon; a rash is quickly spreading on Rosalee's neck where she came into contact with Gilko. At the same time, Nick calls, letting Monroe know about the possible comeback of this so-called Yellow Plague. They quickly put the pieces together just as Rosalee starts to display symptoms. Losing control, she horridly tells Monroe that he needs to mix up the antidote on his own. It's a race against the clock as Monroe tries to make the concoction.
Nick and Hank track down Gilko and bring his unconscious body to the shop. They test the potion on Gilko and prepare it for Rosalee. In the midst of the madness, Hank learns the truth about Monroe and Rosalee's shocking identities - yet another Wesen discovery! In the end, the concoction works... Monroe saves the day! And Monroe and Rosalee finally get that first kiss they wanted.