Someone living in a bubble — literally.
The usual reason is because the Bubble Boy or Girl possesses a weak immune system or other serious illness and simply cannot venture out into the world without protection. Any attempt to do so would prove nearly or completely fatal. So obviously this trope is almost always played for comedy. Either it will set up a situation where characters are expected to treat someone like a woobie when they're all Jerkass, or they'll be in a mobile hamster ball that's used for physical humor. If the bubble is broken, expect the character to be fine. Serious depictions are rarer, but can be good.
Frequently The Woobie as a result.
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A flea-and-tick-powder commercial shows a beagle living in an elaborate network of clear plastic tubes and boxes, apparently intended to keep it isolated from parasites.
Ethan Shields, an immunodeficient Stark-Fujikawa scientist in Marvel 2099 Unlimited, who was also the armoured superhero Galahad... or at least controlled the robot from within his protective forcefield.
Guardian Angel's Barrier Warrior powers in PS238 have effectively made her this. Since nothing even temporarily harmful can reach her, she can't be immunized, and since the barrier keeps all disease away from her, she has never developed an immune system.
Pearls Before Swine: Pig's sister Farina lives in a plastic bubble, though not because of her immune system but because she's a germaphobe. Shockingly, though, she's actually let other suitors like Dilbert and HAGAR THE HORRIBLE inside, which drives her lover Rat insane.
Films — Animation
Several gags reminiscent of this trope are used with Rhino in Bolt, although he's able to leave his ball whenever he feels like it.
One of the orphans in The Cider House Rules, Fuzzy, is confined to an oxygen tent due to his damaged heart and asthma, brought on by fetal alcohol syndrome.
Royd Eris, the captain of the ship in the George R. R. Martin short story "Nightflyers", is this trope in space. He was born on his ship and has never set foot outside it, and when he takes on passengers (which is rare), the section of the ship that they are allowed into is totally cut off from his own section.
Inverted in one of the stories from Palahnuik's Haunted, in which young carriers of lethal viruses are quarantined at a secret government facility so their ailments won't overwhelm everybody else's immune systems. So far as the isolated kids' lives are concerned, it's the same trope: sterile housing, airtight suits to wear outdoors, and no physical contact with other humans unless another kid with the same strain shows up.
The Hitek in Man After Man, due to being crippled by an accumulation of genetic flaws, must spend their lives sealed into life support vehicles.
A similar effect surfaces in the case of Vivenna from Literature/Warbreaker. She spends most of the book shielded from a cocktail of diseases by a magically boosted immune system. When she temporarily loses the magic, she gets very sick very fast.
The Seinfeld episode "Bubble Boy". The Bubble Boy was a bit of a Jerkass though.
On Northern Exposure Anthony Edwards played a man who had developed severe allergies to artificial materials (basically, to US civilization). His whole house was encased in a bubble. At one point he borrowed a space suit from Maurice (a former astronaut) to go among the townsfolk.
Though not quite a bubble, a teenage girl on House who'd just undergone a heart transplant was confined to her sterile bedroom by her germ-paranoid mother.
Star Trek: The Next Generation has an episode where the Enterprise crew found kids in a sterile environment inside an abandoned facility. Subverted in that the kids' altered immune systems killed the surrounding germs, as well as possibly every other life form in that building.
Kenny from Being Human. He is in a fairly large room, so he has some comforts though. However, it is portrayed completely seriously. He comments that what he has is not living, and will walk out of the room when he turns 18.
"Jon" of Delocated makes himself an invulnerable, multimillion-dollar bulletproof bubble near the end of the series to protect himself from the Russian mob.
"The Boy in the Bubble," the opening track from Paul Simon's 1985 Magnum OpusGraceland, drops a mention of "the boy in the bubble" as an example of how "these are the days of miracle and wonder."
The entire quarian race in Mass Effect. Tali, your Quarian teammate, is even more of a woobie than the rest of her people. Several other species are confined to environmental suits in the atmosphere of the Citadel, but presumably they can at least take them off in their living spaces and enjoy each other's company. The quarians, due to their weakened immune systems, must spend long periods of time accommodating themselves (using specially prepared vaccines and suffering lots of side effects) to sharing an atmosphere even with someone of their own species, and generally only take the trouble with children or spouses. Even then they tend to be sick for days after sex. If you get the Golden Ending and reconcile them with the geth, the geth are able to upload into their suits and alleviate their problems immensely.
A girl in ''Growlanser III', though it's more of a clean room than a bubble. One of the game's potential love interests can cure her, after which she can become a love interest herself.
In an episode of Weebl & Bob, a boy in a bubble (named "Bubble Boy") asks if Weebl's clean and if he can use his toilet. However he refuses to come out for fear of "the germs" (that's why he's in the bubble in the first place) and starts urinating in his bubble, and drowns in his own wee.
Cameron from Total Drama is literally labelled "The Bubble Boy", and admits to having an overprotective mom and has never really done much outside of the bubble before auditioning for the show at age 16. He doesn't seem to mind the bubble though, and even cries out for it in one of the challenges. He struggles through the show so that the prize money can go towards having more oxygen pumped into the bubble, but by the end he decides that since he left the show in one piece, he won't need it.
White Knight of Generator Rex keeps himself in a sealed room after an accident that cleansed him completely of the nanites that have infected everyone on the planet. Notable in that it's very hard to sympathize with him due to it being willing. And that he's a big jerk. White Knight explains that since he is the only being on the planet not infected with nanites, he is only person who can be fully trusted to not turn into an EVO and turn on his allies. Given his fear of germs, he probably would be quite happy to stay in his clean room even if it didn't give him a position of authority.
In the Family Guy episode "The Father, the Son, and the Holy Fonz", Stewie ends up one of these after a botched baptism makes him sick.
My Gym Partner's a Monkey has this episode where Adam has to be in a bubble because he was thought of having allergies. His animal schoolmates were even jealous about him.
Sandy is pretty much a Bubble Girl — outside of her Treedome, she's always seen in her air suit, since she's a "land critter" who needs air. Whenever SpongeBob, Patrick, or any other sea creature visits her house, they also become this by wearing a water helmet.
The main characters of Recess ended up in one of these when they faked the symptoms of a severe illness (they were aiming for a more minor one but Gretchen messed up).
The Simpsons episode "Little Girl in the Big Ten" had Bart in a bubble to prevent others from getting sick after being infected with the contagious "Panda Virus" from being bitten by a Chinese mosquito that was in a Krusty Burger toy.
Boog in Fanboy and Chum Chum lived in a plastic bubble during his childhood because he had an air allergy.
Batman Beyond: Scientists develop a special iso-field to envelope people like this. Unfortunatly someone weaponizes this into an impenetrable force field.
Carl becomes a Bubble Boy when a disease is going around town. Part of the reason is because of the Sick Patch the title character made; what started out as a ploy to get out of school went out of hand.
Carl's father has also stated that he used to be one.
On KaBlam!, a Sniz and Fondue cartoon had Fondue moving into a sanitized bubble habitat after being freaked out by a documentary on skin parasites Sniz showed him.
David Vetter was the inspiration for The Boy in the Plastic Bubble, and thus many of the works that were inspired by it. He lived until the age of 12 when he died from a failed bone marrow transplant. The psychological effects of being a 'bubble boy' were... not pretty.
In some places you can pay to be encapsulated in a giant hamster-ball-style bubble and run along plains for a set amount of time. This is a sport called Zorbing.
Leukemia patients who undergo bone marrow transplants have to live in extremely sterile conditions during the period after their own faulty stem cells have been eradicated, but before the donated marrow has generated new white blood cells.