Shido Itsuka & Shinji Takamiya[]
Mio was first mentioned by Shido to Mana when he lost control of the Spirit powers sealed within his body. But during the events of Mukuro Planet, Shido could only remember the affection she had for him.
After using <Michael> in an attempt to regain his memories of Mio, it is revealed that Shido, in his previous incarnation as Shinji Takamiya, found Mio after a Spacequake and named her after the 30th, the day where they first met. It was through her time living with Shinji that Mio grew an understanding of the concept of love. Shinji's death at the hands of being gunned down by Westcott devastated Mio, causing her to finally realize how much the boy means to her and how the boy fills her ashen world with vibrant colors.
Despite personally creating Shido as Shinji’s reincarnation, Mio deep down understands that Shido will never truly be the same person, and Shido suggests that she really just wanted to create someone capable of killing her. Mio ultimately sacrifices herself to save Shido from Westcott, admitting that she loves him but still prefers Shinji.
Tohka Yatogami & Tenka[]
Mio inadvertently created Tohka while experimenting with a new method for creating Sephira Crystals. While initially shocked at her creation, Mio ultimately concluded that she was too much of an unknown variable and had to be removed. However, her malice ended up provoking the contemporary Inverse Spirit Tenka into immediately attacking her in self-defense. While Mio praised Tenka's strength, she ultimately still defeated her and reduced her back to a Sephira Crystal. Still, Mio couldn't bring herself to kill the only other Pure Spirit in existence by destroying the Crystal, instead choosing to embrace her as her daughter.
In the Game Over Timeline, Mio showed that, despite embracing Tohka as her daughter, she is still willing to kill her to retrieve her Sephira Crystal. However, after Tohka managed to resurrect herself from her Sephira Crystal following her first death at Mio's hands, she openly praised her, citing she always believed she would be the only one capable of opposing her. Ultimately though, Mio once again killed Tohka, this time using <Ain> to ensure she wouldn't resurrect.
After obtaining Mio's Sephira Crystal, along with some of her memories, Tohka theorized that another reason why she spared her was because she hoped Tohka would be the one to grant her secret death wish. Even after dying, Mio's will would influence the world to recreate the Spirit Formula a year after Tohka's disappearance, reconstructing her daughter while using the latter's parallel world counterpart to speed up the process.
Mana Takamiya[]
Mana first met Mio when Shinji had just taken her in and was initially suspicious as to why her brother was with a girl who, at the time, was half-naked. However, Mana seemed to quickly open up to her, attempting to find her clothes when she sneezed. When dressing up, Mio would generally use her powers to copy Mana’s outfits. Afterwards, Mana continued to help Mio integrate herself into society, causing the latter to refer to her as her "Master". Aside from this, the two also seemed to have been good friends. When Westcott takes Mana hostage, Mio agrees to return to him in exchange for Mana’s safety, only stopping when Shinji insists that Westcott cannot be trusted to uphold his end of the deal. Mio’s doppelgänger Reine became furious when she realized that DEM had sacrificed Mana’s lifespan to enhance her power as a Wizard.
In the Game Over Timeline, while Mio showed no hesitation to kill anyone else other than Shido, she openly stated that she did not want to fight Mana. Instead, she teleported her away from the battlefield, even restoring her memories that had been sealed away by DEM.
Kurumi Tokisaki[]
Despite saving Kurumi from the hands of a berserk Spirit, Mio was still willing to trick Kurumi into becoming a Spirit under the premise of being an ally of justice who was saving the world from Spirits. When Kurumi found out about the deception after accidentally killing her best friend, Mio apologized for her actions and explained her identity as the First Spirit and how other Spirits were actually humans given a fraction of her power. However, she still refused to explain her motives, only stating that she bears no grudge against her but cannot stop until the completion of her goal.
Despite killing Kurumi in the Game Over Timeline, she still offered her thanks for everything Kurumi had done and respectfully closed her eyes. In the True End Timeline, Mio acknowledges Kurumi's crafty nature, remarking that Kurumi must have taken precautions to prevent her from reclaiming Zafkiel's Sephira again.
Sir Isaac Ray Pelham Westcott[]
Westcott is Mio's creator, having brought her into the world through his <Spirit Formula>. Mio is aware of his possessiveness towards her, but she never returns his affections. On the other hand, she doesn't seem to hate him either. Even after he killed Shinji, she never even bothered taking revenge on him, only killing him in the Game Over Timeline to retrieve the stolen piece of Nia's Sephira Crystal. In the True End Timeline, Mio finally told Westcott that he was never her "favorite person" as a way of freeing him from his suffering.