Missy Cooper is Sheldon's fraternal twin sister, who is ironically the direct opposite of her brother in many ways (besides being a female, she is not above physical confrontation, is very charming and amicable, as well as possessing a very cheeky sense of humor).
Missy's main appearance is in "The Porkchop Indeterminacy" (S01E15). When Leonard, Howard, and Raj find out Sheldon has a sister and that she is quite attractive, they fall over each other trying to get her attention. Raj is inspired to begin taking an experimental medication to overcome his pathological shyness.
When Sheldon states that he'll decide who Missy dates (desiring that she reproduce with a smarter version of him, which he dubs "Sheldon 2.0"), she decides to speak with him privately. She tells him that she is fine with him acting like a brother who cares about her, but if he tries to tell her who to sleep with in her bed, they are gonna go "round on round" like they did when they were children. This flies over Sheldon's head and he suggests Missy donate her eggs and cryogenically store them until he finds the right sperm donor to fertilize them before implanting them into her body. By this act, he suggests, "everybody wins". Missy then begins painfully squeezing her brother's testicles until he withdraws the statements.
Missy finds more of an ally with Penny, who has become slightly immune to the quartet's geekiness, as well as helps Missy extricate herself from them and lets Missy hang out in her apartment. Leonard, Howard, and all knock on Penny's door to ask Missy out, but they fail in the end. When Raj goes to ask her out, she says that she was waiting for him to show up and calls him a cutie-pie, but Raj's medication starts wearing off so he is unable to talk to her and leaves looking sad.
Before she leaves, Missy tells Sheldon that she is proud and reveals that she brags to her friends about her brother "the rocket scientist", which sparks him to correct her that he's a theoretical physicist, noting the difference. After she leaves, Sheldon mutters back to his apartment saying that being a rocket scientist is beneath him.
Sheldon mentions her in "The Jiminy Conjecture" (S3E02), saying "I grew up with an older brother and a very contentious twin sister."
Sheldon's family pedigree, depicted briefly in "The Cruciferous Vegetable Amplification" (S4E02), shows an older brother as well as his twin sister.
In "The Cooper Extraction" (S07E11), Missy is about to give birth to a baby in Texas. Since her husband is recovering from a terrible motorcycle accident, Sheldon has to go back to look after her. She does not appear on screen in this episode, only a scream as she gives birth is all that is heard from Missy.
In "The Matrimonial Momentum" (S9E01), Mary Cooper mentions that since Missy is married and their brother is dating a "whore", she wants Sheldon to keep her grandmother's ring which she gave Sheldon for Amy.
- Father: George Cooper Sr.
- Mother: Mary Cooper
- Brother: George Cooper Jr.
- Twin Brother: Sheldon Cooper
- Grandmother: Meemaw
- Grandfather: Pop-Pop
- Uncles: Uncle Carl, Uncle Edward, Uncle Roger; There is another uncle who gave children gifts like Santa and was not arrested in Oklahoma for his actions.
- Aunt: Aunt Ruth
- Husband: Unnamed
- Son: Unnamed
- She calls Sheldon by his nickname, "Shelly", as does their mother.
- When they were kids, Sheldon turned her Easy-Bake Oven into a furnace for baking ceramic semiconductor substrates for homemade integrated circuits to make a robot to defend his room from her.
- Missy tells people Sheldon is a "rocket scientist", which insults him because he is a theoretical physicist, which he views as much more prestigious and tells her that she might as well tell people that he is a toll collector at the Golden Gate Bridge.
- Despite their differences, Missy is very proud of Sheldon and his accomplishments, constantly bragging about her "brother the rocket scientist" to her friends, a compliment that Sheldon is deeply offended by.
- When Leonard offered Missy to stay with them, she reveals that Sheldon does not like company and he used to send his imaginary friends home at the end of the day when he was a child: he denies it, saying that they were "imaginary colleagues".
- She once had a dog who made strange noises which she later had put down.
- It is revealed in the Pilot that she is a hostess at Fuddruckers when Sheldon is expressing concern of "committing genetic fraud" about donating sperm at a high-IQ sperm bank ("I have a sister who has the same basic DNA mix who hostesses at Fuddruckers.")
- Her full first name may be Melissa, as Missy is a common nickname.
- Her mother dismisses her as "dumb as soup" in "The Luminous Fish Effect": though she is likely nowhere near as intelligent as her brother, she seems witty, presentable, and funny. Though Sheldon also mentioned in "The Cooper Extraction," it took Missy six years to graduate from high school, implying her mother's comment about her intelligence isn't wholly inaccurate.
- When she first meets the gang at Caltech, she tells them that she spent nine months with her legs wrapped around Sheldon's head.
- She used to obligate Sheldon to do whatever she wants by pressing his testicles. She still does it when she gets mad at him.
- Sheldon considers her, with his help in choosing a proper and approved-by-him mate, the future mother of a "Sheldon 2.0". She, however, doesn't see it that way.
- She is taller than Leonard, Penny, Raj and Howard, like her brother.
- In the episode "The Cooper Extraction", it's revealed that Missy is married and was having a baby.
- In one episode, Sheldon mentions that she had a guinea pig called Snowball, which ended up bursting into flame when Sheldon put him in a home-made CAT scanner.
- Her husband's name and her son's name are both unknown.
- It still hasn't been confirmed which of the Cooper twins (Missy or Sheldon) is the older one, and by how long.