- "So what if she is a Blue? We'll still keep her."
- "We can't do that. She's on the other team, she'll kill us in our sleep if we keep her."
- "Do I get to do that? That would be awesome!"
- —Sister in Yellow Fever
Although Sister doesn't have as many relationships with other characters compared to the main cast, she has developed more than most other characters have.
Sister seemed to enjoy being on Blue Team and developed some unique relationships with her comrades.
Church and Sister have not interacted much, but Church once referred to her as a freak and a whore. According to Epsilon, Sister seemed to like him.
Sister has a good relationship with Tucker, though he seems more interested in her than she is in him. Being a womanizer, he frequently attempts to hit on her, and expresses jealousy and frustration when Doc forbids him from watching her physical examination. Tucker promises to protect Sister when she was told about and frightened by O'Malley in The Nesting Theory. She likes Tucker enough to kill her own brother for killing him, during which she shouted, "I liked [Tucker]! He was nice to me!" in the "Fight! Fight!" ending of Episode 100. In The Installation, Tucker tells Grif "I fucked your sister", and in A Real Fixer Upper he claimed "Your sister was my bitch if i remember correctly." to Grif, but this might have been comebacks to Grif's insults.
Caboose gives Sister a tour of Blue Base when she joins the Blues and the two seem to easily relate with one another. Caboose seems to get along with her in the time they've been shown together, possibly because both have a low intelligence. Notably, both are colorblind.
Tex does not hold Sister in high regard, and it is heavily implied that she is envious of Sister, as she views her as a replacement. When asked what she and Tex talked about when they spoke one-on-one in Terms and Provisions, Sister states that she was told that if she tried to become more popular than Tex, Tex would talk about her behind her back, turn everyone against her, and make her cry.
However, seeing that Sister is unfazed by Tex's warnings, along with her "You know, girl stuff!" statement at the end of her description, Sister probably does not share the same feelings towards Tex. She also says Tex is a "badass" and is "kinda hot".
Sister's first meeting with Junior was less than flattering for the little alien, as she mistook him for a dog but quickly corrected herself by describing him as a "kid that looks like a dog." During her trip through the caves, she was slightly supportive of Junior, cheerfully calling attention to him as he fell behind and showed some care towards him.
Flowers is responsible for having Sister sent to Blood Gulch, after corrupting Vic. According to Sister, she was sent to replace Flowers after his death. When she meets him in the caves, Sister treats him kindly before realizing that he's supposed to be dead. Flowers and the Green Alien then take her, Doc, and Junior hostage when Omega's assault began. Despite this, Sister suggested that Doc help him after Omega leaves his mind.
Washington and Sister only have one brief conversation together in Reconstruction: Chapter 2. Sister takes an obvious dislike towards Wash, as she believes him to be a cop. Wash likewise views her as annoying, irresponsible, and possibly insane, but manages to maintain his composure.
Because she is color blind, Sister originally mistook the Reds as her new team. While they found her odd, her relationship with her brother allowed her to interact with the other Reds.
Sarge thinks she is a tramp. When she first arrived in Season 5, Sarge questioned her being in the army, as she was female, and asked if her gun "shot brownies". Due to never mentioning she was colorblind or a Blue, Sarge ended up being buried alive because of her. In Reconstruction, he refuses to kill her, even though she was the final Blue left at Blood Gulch Outpost 1A, simply because she is female. Sister thinks that because Sarge is old, he is also "very gross."
Sister thinks he is a nerd (and also thinks the fact that he is scary is "kinda hot"), while Simmons thinks she is unintelligent and annoying. Simmons additionally does not approve of her insults towards his intellect and quickly takes offense to them. He is, however, heavily fascinated by some of the things she reveals about her family, such as the fact that her and Grif's mother is in the circus, and even asks her if he could record everything she says. Later in Season 5, whilst the Reds were down in the caves beneath Blood Gulch, Simmons was interested in seeing Sister naked during her physical examination with Doc, which was displayed on the large computer screen.
Sister and Grif have a stereotypical brother-sister relationship. She is very fond of her brother, having joined the army for the sake of reuniting with him and not being left alone. Even when she has not seen him for years, Sister stands by her brother's innocence when he and the rest of the Reds and Blues are accused of murder, claiming a government conspiracy and insisting that he is a "total softy." Likewise, when Sister seems to be in danger, Grif will take action and do what he can to ensure her safety. For example, in the "Fight! Fight!" ending of Episode 100, when Grif assumes Tucker to be threatening her, he kills him. When she appears to be dead in Biting the Hand, Grif grieves for her.
However, when he discovered that she was in fact alive and just naked, he calls her a slut, heavily enraged upon seeing her "embarrassing the family." In fact, she is often an embarrassment to Grif, particularly when divulging information about their mother, and he instructs her not to embarrass the family when she switches to the Blue Team in Episode 85. When Grif gets frustrated at her various inappropriate statements in Mr. Red vs. Mr. Blue, she screams at him, claiming he is just like their mother and father. When Lopez claims to have killed her in Relocated: Part Three, Grif doubts his claims. It is later revealed that Sister merely passed out. According to Doc's O'Malley persona, Grif believes their parents loved her more than him.
In the underground caves, Sister seemed to anger Lopez while translating for him, but seems to be one of the few who can understand him. Later on, Lopez claims to have killed Sister after Sarge left Blood Gulch. It is later revealed that he had merely choked her until she passed out.
While the two don't interact much Sister crushed Donut with her ship when she first arrived at Blood Gulch.
When Doc first met Sister in Season 5, he was fascinated by her flexibility, but nothing else. Any other interest in her is lost after being stuck with her and Junior in the canyon's caves in Loading... He thinks she talks far too much and is tired of hearing all of her "stories." Sister, on the other hand, does not seem to have a noticeable opinion of Doc. She also convinced him to help Flowers after Omega left his mind.
Sister was initially annoyed with Andrews, as she and her cameraman were filming on top of Blue Base, and at one point mistook her for the fire marshal. After Andrews cleared the air, Sister agreed to an interview. She even admitted she was attracted to the reporter, which she described it as a "bi phase" returning. Though she was willing to do the interview, she was left miffed by Andrews's insinuation that Grif was somehow involved in the recent murders after the Chorus incident, insisting to the reporter that he was "a total softy," and continued to defend him even after the interview had wrapped.