- "If Simmons blows up Blue Base, Sarge is gonna be really mad."
- "Sí. Él es estúpido como ése."
- —Lopez insulting Simmons' intellect
- "I’m worried about him..."
- "Sí porque usted es estúpido como ése."
- —Lopez insulting Donut's intellect in Bon Voyage
Lopez's relationships with the other characters seems to be on rough terms. Interestingly, while Lopez hates the other members of the Blood Gulch Reds and Blues, he still seems to care about them to the point where he'll save them. One point is when he calls Lopez 2.0 an 'annoying moron', implying that although he hates the others, he won't go to extremes like Lopez 2.0 did and try to kill them.
As time passes, Lopez realizes that all of the Reds are fools and has developed rough relationships with them.
Due to the fact Sarge built and programmed him personally, Lopez initially loved him like a father but grew to dislike him later on due to his insane plans and absurd ideas. Usually, he claims he would prefer to die than listen to him and during Reconstruction when Sarge contemplated leaving, Lopez begged him to go (though Sarge thought he was asking him to stay). Sarge eventually leaves and Lopez initially rejoices but later becomes disappointed upon realizing that he was alone.
Afterwards, he receives a call from Sarge asking him to come to Valhalla and help him and the Reds build a Holographic Projection room. Lopez was reluctant at first but eventually went to help. When stranded on Chorus, Sarge still tries to make conversations with Lopez, but the latter joyfully insults him, knowing that Sarge will not understand. At this point, while still annoyed by Sarge, it is shown that Lopez seems to have grown used to Sarge's antics and found a way to tolerate him. When Lopez is reactivated at F.A.C. Outpost 37, Sarge welcomes him back to the living, though Lopez remains unhappy about it.
Lopez dislikes Simmons' attitude, seeing him as racist and as much of an idiot as the rest of the team. Despite this, he is still willing to build machines for him and lends support during the confrontation with the Meta, including saving his life. Simmons also was able to relate with Lopez by explaining he is part cyborg and shows to have a mild understanding of Lopez. After Lopez is left behind at Valhalla, Simmons seems to see Lopez as intelligent, saying the difference between Lopez and Lopez 2.0 was that Lopez 2.0 "wasn't very smart."
Lopez hates Grif simply because Sarge programmed him to. When Sarge orders him to execute Grif, Lopez is extremely grateful and happily complies. Considering Grif's nature, it is likely that Lopez hates him naturally as well. Grif, however, seems to like Lopez, though is annoyed by the fact that Lopez doesn't speak English and once claimed he was faking it. In Teaming with Problems, Grif remembers Lopez as one of the captives after Simmons only mentions Donut, Washington, and Sarge.
In Capital Assets, when Lopez tells the Reds at the armory to ensure Jensen never drives a car again due to her terrible skills, Grif (and Simmons) reminds him that they still don't understand him and just "assimilate", infuriating the robot. Their relationship is made worse in Armonia, Part 1, where Grif starts the Pelican's engine when Lopez is fixing it, getting him stuck inside. As Simmons removes him, an enraged Lopez uses his headless body to strangle Grif. Despite this, Lopez has shown himself capable of working with Grif when the situation demands it, such as in Objects in Space when he informs Grif of what's happening to their friends, where it's revealed that Grif had finally learned Spanish. Although later, in Red vs Red, Lopez attempts to communicate with Grif so he wouldn't be thrown into the ocean but is ignored, with Grif pretending he no longer knew Spanish.
Of all the members on the Red Team, Donut is perhaps the one Lopez hates the most especially since he's the one that made him into a scarecrow. Like Simmons and Grif, he finds Donut highly annoying due to his idiotic nature and his terrible attempts at translating Spanish. In Recreation, after the Meta attacked, when Donut appeared in Red base, Lopez suggested to Simmons that they kill Donut "in case" he was the Meta in disguise, but if not, Lopez still suggested they kill him nonetheless. Donut later reactivates Lopez in Season 11, much to his dismay, and brings him to Chorus, where Donut still pretends he understands what he's saying, upsetting Lopez.
When Lopez's head is shot off in Season 12, Donut expresses concern for him, though Lopez saves Donut shortly afterward, implying he doesn't entirely hate him. During Season 13, Lopez's relationship with Donut changes from hatred to tolerance. They work together for the majority of the season with Lopez having no major complaints about doing this. In fact, it is possible that Lopez now prefers the company of Donut more so than the rest of the Blood Gulch Crew. In The End, Donut happily tells Lopez that he loves him after mistaking Lopez's request that his parts be recycled should he be destroyed in the upcoming battle with Charon forces. It is worth noting that Lopez didn't make any attempts to correct Donut then, suggesting that Lopez was moved by Donut's sign of affection.
During his time on Blue Team, Lopez seemed to tolerate the Blues. However, he later considers them being as foolish as the Red Team.
Lopez and Tucker seem to be able to work together on decent terms, mainly when they and Sheila work together to get the Red Team to turn off their headset radios. When Lopez and Sheila revealed they were leaving the team, Tucker couldn't believe it. It's also shown that Tucker is one of the few characters that understands him. In Season 11, Lopez saves Tucker from a Federal Army soldier, and when he is shot, Tucker displays extreme concern for him. Arguably, out of all the Blood Gulch soldiers, Lopez seems to tolerate Tucker the most.
Lopez has little interaction with Church, but he shows to dislike him due to being "constantly possessed and blown up," which eventually caused him and Sheila to create their own army, which was actually because Future-Church gave them the idea.
Caboose is Lopez's rival for Sheila's heart and dislikes him for it, but Lopez shows no contempt for Caboose for this reason. He hates it when Caboose dances the robot believing it is racially offensive.
When Lopez and Shelia first met, they instantly fell in love, having a brief, affectionate talk before Lopez is shooed off by Caboose. Afterward, Lopez sings a love song for her when making the Red's turn off their headset radio and they soon developed their own army. After O'Malley/Doc kidnapped him, Lopez and Sheila have had little to no interaction with each other, but he's shown to still be in love with her when seeing her in Why Were We Here? During later seasons, however, he is completely unaware of Sheila's presence in Valhalla while he was there, thus making it unknown if he still holds these feelings.
Lopez and Sister have had very little interaction with each other. After Sarge leaves Blood Gulch, Lopez strangles Sister and later tells Sarge of their victory, but it is later revealed that Sister survived. It should be noted that Sister was one of the few characters that could understand him, though Lopez blatantly tells her that "[her] Spanish sucks.", after Sister attempts to talk to him in Spanish.
Lopez has little interaction with Wash apart from being shot by him and when the latter is furious when Donut's "rescue team" only consist of Doc and Lopez. When captured by the Federal Army of Chorus, Washington asks about Lopez and Freckles' whereabouts, leading to Lopez being reactivated. During his reboot in the Federal Army camp, his HUD displays Donut and Sarge as "idiot" and "loud idiot", but simply refers to Washington as "Agent Washington", suggesting he respects him more than he does Donut and Sarge.
Lopez has had little to no interaction with Epsilon, though, despite this, Epsilon still had memories of him while he was in the storage unit.
Despite being kidnapped by O'Malley, Lopez accepts any order given by him and manages to work with him, as he defends Zanzibar from the Reds and Blues and even builds him a robot army. However, Lopez's relationship is more strained with O'Malley than with Doc, as Lopez does insult him, trick him to insult himself, and corrects his spelling mistakes from time to time.
Lopez seems to get along very well with his successor, even referring to him as "kid" at one point. He also tells Lopez 2.0 all about his history with the Reds and teaches him to ignore orders and insult Sarge in Spanish, much to the latter's enjoyment. Lopez initially wanted himself and Lopez 2.0 to join forces against the teams, but the latter betrays him. After Lopez 2.0's death, Lopez takes the latter's body and refers to him as an "annoying moron." When Lopez returns to Crash Site Bravo, he finds Lopez 2.0's giant body and refers to him as an "asshole," further expressing his distaste for his successor.
While the two are never seen interacting when Doc first comes to Blood Gulch due to being possessed by Church, Lopez is partly responsible Doc getting infected as Doc was on the radio to report the vehicle he and Sheila made. After Lopez is kidnapped by Doc/O'Malley, he becomes their minion in the mission to destroy the Reds and Blues and take over the universe. His relationship with Doc seems decent and friendly when compared to Omega's. Doc seems to understand Lopez, he agrees with Doc more than O'Malley, and it's suggested that Doc got a g-mail invite from him. Lopez is later shown to be angry at Doc for forgetting about him during Season 5 but seems to forgive him by Season 11. Doc and Donut bring him to rescue those at the crash site and Lopez shows concern when Doc disappears in Ready…Aim…, and later brings it up when the teams are explaining their experience with the Teleportation Grenades to Carolina, reminding them that they also teleported Doc. However, due to them not being able to understand, they simply ignore him while Donut misinterprets his words. However when Doc returns in Temple of the Key, Lopez doesn't seem to notice his return or doesn't care that he's back.
Lopez has no direct interaction with the Meta apart from detecting him as an immense danger, and shooting him with a Missile Pod. He, along with Simmons and Donut, defends the Red Base from him before trying to escape.
Lopez has little interaction with Locus, though, like the other Blood Gulch Crew members, he shows a fear towards him. Lopez also believes Locus to be a douche for capturing them and for saying that machines are meaningless, proceeding to call Locus insane. When Locus replies that he is not insane, Lopez becomes extremely frightened at the fact that Locus can understand him and begs Locus not to kill him.