The episode starts with Blossom's in bed sneezing, having chicken pox with lots of red spots, like humans. As the pain is hurting Blossom, Nancy is taking care of Blossom. Brick comes by one day and gives Blossom a get well card and says he'll fix her hot bowl of soup. Blossom says that's so sweet of him. Blossom is about to kiss Brick, but Brick says that's a bad idea since he could get sick too. Blossom says sadly smiling right. Blossom is really hurt by her chicken poxs.
Later, Brick tries to make soup for Blossom. However, he doesn't know how to make it. He asks Butch, Boomer, Bubbles and Buttercup for help. They don't know either. They still make it anyway poorly, and in a disgusting way.
Brick gives it to Blossom. Once she drinks a sip, she spits it in his face, saying it's terrible. When The Rowdyruff Boys along with Bubbles, and Buttercup fight a monster, Nancy, who is wearing a safety jumpsuit (to avoid getting chicken pox from Blossom), takes Blossom with her to give Blossom some soup. As take go to the store, Blossom accidently sneezes on several people at the store, giving them "powerpox" immediately.
The next day, Blossom still has chicken pox. While Blossom's asleep in bed, The Rowdyruff Boys along with Bubbles and Buttercup see a shocking news report on TV, and says Townsville is getting a unusual diease call powerpox and suddenly all the citizens in Townsville who have powerpox, become a monster with powerpox and starts sneezing, destroying Townsville in the process.
The Rowdyruff Boys along with Bubbles and Buttercup go and fight the Giant However, in the process they develop starting to get Powerpox growing weaker and turning into a monster
Meanwhile, Blossom wakes up from bed, and gets up for a glass of water for her throat. As she drinks water, she sees the news report on TV and sees a giant monster destroy Townsville. Blossom realizes she cause this problem, and goes to save everyone in her clothes. Then when she sees the Giant Blossom battles it. But she is a bit weak due to her pain of the poxes on her. Though, she manages to defeat it in the end. This recovers everybody in Townsville whi had Powerpox, to be back to normal. Including, Brick, Butch, Boomer, Bubbles, and Buttercup to be revived from the diease.
Later, Professor and Anna Goldman discover that drinking vegetable oil gets rid of Powerpox painlessly. This works, recovering Blossom to her normal beautiful self.