While Ash, Misty and Brock continue to make their way for the Violet Gym, they find themselves looking for a place to spend the night in a quiet area called Happy Town. Tired, hungry, and dirty, Ash knocks on the door of a locked Pokémon Center and, to his surprise, is greeted by a Blissey. After noticing Ash's hunger, Blissey tries to give Ash some sweets, but ends up spilling it on Ash. While washing off, Blissey suggests that she washes his back, but ends up scratching him, and while she tries to attend to the scratch, she puts too much alcohol on him, and at the end of the sequence of events, he is in a full-body cast for one scene. Nurse Joy wakes up eventually and apologizes for her Blissey's trouble.
Outside, Team Rocket is just as hungry as Ash's party. James devises a plan to sneak into the Pokémon Center and steal some Pokémon and some food, but once they get inside, they find themselves in an empty kitchen with nothing to eat. Meowth finds a parsnip in the fridge, but refuses to share it and runs off. Jessie goes looking for him, but finds a Blissey in the hallway. The Blissey tackles Jessie in joy; Jessie at first thinks that she tackled her to stop her, but then notices Blissey's necklace is shaped of the top of a broken egg, which Jessie pulls out the bottom half that she kept with her to it and connects the pieces. She then remembers Blissey.
Jessie explains James and Meowth that when she was young, she wanted to become a Pokémon Nurse, but she could not get into a regular nursing school. She noticed a flyer for the Pokémon Nurse School, which was intended only for Chansey, and decided to go there, despite being advised not to. Jessie was the only human in the class, the rest being Chansey. She was quite competent at nursing, and helped out a Chansey who kept messing things up by showing her how to wrap bandages, among other things. The two quickly became friends. While Jessie was good at most nursing skills, not being a Chansey she could not resist Sing, and fell asleep when she was supposed to be singing sick and injured Pokémon to sleep, causing her teacher to become very annoyed with her.
She gave up on nursing and failed to graduate, but her friend Chansey did. On the graduation day, each Chansey was given a nurse's hat and an egg-shaped pendant. As Jessie was leaving, she was confronted by Chansey, who first tried to give Jessie her hat, but Jessie refused to take it, so she gave Jessie half of her pendant so that they both had something to remember each other with.
Overjoyed to see her friend again, the evolved Blissey satisfies Team Rocket's hunger by giving all of the food from the Pokémon Center storeroom. Jessie was unsure if they should take all of the food, but they took it anyway.
The next morning, Ash and his friends found that there was only a tiny amount of food left in the Pokémon Center. Ash complains to Nurse Joy about the lack of food. Nurse Joy checks the storeroom, only to find that it is empty when it was full the day before. Nurse Joy reviews the security tapes to see who took the food, only to find that it was Blissey who took the food. Nurse Joy asks Blissey to explain why she took the food, and says that it could end Blissey's career as a nurse.
Watching the scene through their binoculars, Team Rocket devise a plan to get Blissey out of trouble, and they decide to go back and tell them they tricked Blissey into giving them food. They land their balloon in front of the Pokémon Center and announce over a megaphone that they "accidentally" dropped all the food that they "stole". Once they have everyone's attention, they demand that all of the Pokémon in the Pokémon Center be handed over to them, or they won't return the food. While Ash and Nurse Joy argue with them, Blissey comes outside and runs to greet Jessie. Jessie pleads that Blissey not reveal their friendship, and in an attempt to save Blissey's job; Blissey doesn't care and continues towards Jessie, who she sends out Arbok and Lickitung to keep Blissey at a distance, but even after this, Blissey still wants to be with Jessie, so Jessie forces herself to order Arbok and Lickitung to attack Blissey. After they attack Blissey, Jessie yells at them, because they weren't supposed to hurt her.
However, Blissey is quickly back on her feet and walks toward Jessie again, still unaware of why Jessie wants to keep her away. Jessie then orders her Pokémon to attack Blissey again, but this time specifies lightly. Even after that, Blissey limps toward Jessie, refusing to turn away. Then, Jessie shoots the ground with a rocket launcher, and threatens to hit her with the rocket if she comes any closer. James begins to insult Ash because he's letting a Blissey do all the fighting, and then Meowth uses a pair of grabbers to steal Pikachu. Pikachu immediately uses ThunderShock to release himself, zapping Team Rocket.
Nurse Joy then runs to Blissey and apologizes for doubting her. Blissey then looks to Jessie, who puts her finger over her mouth to symbolize that it's a secret. Still hungry, Ash sends out Squirtle and Chikorita to retrieve the food. Pikachu uses a Thunderbolt on Arbok, Chikorita uses a Vine Whip on Lickitung, and Squirtle blasts a Water Gun at Jessie, James, and Meowth, who run to the balloon right after the attack, but Chikorita uses a Razor Leaf to cut the food from the balloon and to put a hole in it, sending the food to the ground and sending Team Rocket blasting off again into the ocean.
Blissey is then shown finally serving a whole meal to Ash and his friends.
The episode ends with Team Rocket in the ocean on their capsized balloon basket, pleased with themselves that they helped Blissey, but depressed that they didn't get any food.