Koyomi wakes up just to find he is in an unknown location held captive. It happens to be Hitagi that captured and imprisoned him. She says she is doing so in order to protect him. Hitagi also takes this opportunity to tease Koyomi, which she takes great joy out of doing so. Going back to the morning of the day, Koyomi is involved in a short fix with Tsukihi after hearing that Karen is out, assuming she is making trouble. Koyomi then remembers Nadeko's invitation to her home in the past, so he decides to give Nadeko a call to see if she is free and wants to hang out with him. While on the way, Koyomi stumbles across Mayoi and decides to spend some time with her first. They talk for a long time while Mayoi gives Koyomi some friendly advice. Mayoi says that she will come back when she needs his help and that she will tell when she will leave for good. Koyomi remembers that Oshino said that same thing to him before leaving the town.

On the same day, only a while after parting ways with Mayoi, Koyomi arrives at Nadeko's to spend some time playing with her, despite learning that her parents are not home. Nadeko is seen styling a different hairstyle than what she previously had. They spend their time talking and playing games. Nadeko becomes frantic after hearing her mother come home because she did not tell her that Koyomi was coming over. Koyomi leaves Nadeko's house and then decides to call Suruga about her asking Koyomi for help in cleaning her room. On his way to Suruga's house, Koyomi meets his sister, Karen, who is in a rush doing some "community service" before leaving in a hurry after receiving a phone call. Koyomi then visits Suruga to find an unexpected sight.

Koyomi stumbles on an intriguing figure who introduces himself as Deishū Kaiki on his way back from Suruga's house. Koyomi then meets Hitagi coincidentally on the street. They start to walk with each other but when Koyomi mentions that he has met Kaiki, Hitagi knocks him out. Back to the present, Hitagi confesses Kaiki was a con man who deceived her mother and is a dangerous person she wants him to avoid at all costs; this being her reason for imprisoning him. Koyomi then receives a text message from his younger sister asking for help. After seeing the text, Koyomi breaks free from the handcuffs with the help of his vampire strength. Hitagi still does not want Koyomi to leave and tells him that she is willing to fight if he does not comply with her. There is a phone call and Hitagi answers it. Hitagi is frantic and seems to be at the mercy of the speaker. After the phone call, Hitagi agrees to let Koyomi pass without a fight. When Koyomi asks who the caller was, Hitagi states that is was Tsubasa.

Back at his house, Koyomi meets Tsubasa who is helping Tsukihi tend to a feverish Karen. It turns out that Tsubasa has been helping Karen with her "mission". Koyomi gets angry at Karen for doing something dangerous and getting assistance from Tsubasa without his knowledge. Tsubasa and Koyomi then go to his room to talk about what happened. After talking with Tsubasa, Koyomi goes to take a bath. While taking his bath, Shinobu emerges from his shadow. Koyomi is shocked to find that Shinobu is actually very talkative. Shinobu then tells Koyomi that Karen was inflicted by a lethal, supernatural bee. The bee sting causes an extremely high fever and makes the inflicted person feel as if they are on fire.

Koyomi learns from Tsukihi and Tsubasa that Karen tried to confront Kaiki by herself. Karen is inflicted with the poison by Kaiki during their confrontation and Kaiki escapes, leaving Karen paralyzed on the floor from the poison. After walking Tsubasa home, Koyomi tends to Karen's fever. Karen tells Koyomi to leave her alone because she does not want to get him sick too. Koyomi then goes to the bathroom to ask Shinobu if there is any way to transfer Karen's fever to him. Shinobu says there is a way but she does not recommend it because it requires an unusual ritual.

Koyomi only managed to drain half of the poison in Karen's body, and although she was not completely healed, her fever has become slightly diminished. On his way to Hitagi's house, Koyomi stumbles on Mayoi again and confides to her about his sister's situation. Upon arriving at Hitagi's house he finds out that Hitagi managed to arrange a meeting with Kaiki and is preparing herself to enact revenge on him. Koyomi explains to her about Kaiki's encounter with Karen and convinces her to not confront him without his help. Back at home, Koyomi learns from Tsukihi that Karen is missing, and worried that she might have left to face Kaiki once more, he asks Shinobu's help to find her.

Thanks to Shinobu, Koyomi manages to find Karen and after a serious fight between them, he convinces her to let him deal with Kaiki by himself. Later that day, he and Hitagi come face to face to Kaiki, but they hear from him, much to their surprise, that he is already leaving the city and Karen should recover in a few days. After letting off all anguish she harbored on him all those time, Hitagi lets Kaiki leave unharmed, and claiming she can finally move on with her life, she asks Koyomi to spend the night with her. In the next day, Koyomi returns home to find that Karen is already fully recovered, and both his sisters leave in a hurry, claiming that there is still work for them to do, due to all the damage Kaiki left behind among their classmates.

Koyomi is concentrated on his studies when he is interrupted by Karen who, much by his surprise, is wearing her sister Tsukihi's clothes, displaying an air more feminine than usual. Karen asks Koyomi to introduce her to Suruga knowing that she is friends with him, but he refuses without giving a reason, fearing that she would make a move on his sister. Karen then challenges her brother to a contest, making him promise to comply with her request if he loses. Koyomi then chooses the contents of the challenge - she would let him brush her teeth for five minutes without resisting, which she accepts. Surprisingly, both start getting more and more aroused as Koyomi brushes Karen's teeth until Tsukihi barges in demanding an explanation. Despite fearing what punishment Tsukihi has in store for them after she leaves and Koyomi accepting defeat, Karen asks him to continue from where they stopped.

Koyomi sets for Suruga's house to introduce Karen to her as he promised. On their way they meet a woman introducing herself as Yozuru Kagenui, asking for directions. Koyomi asks for Tsubasa's help on his phone and learns from her that she is asking for the location of the same building Oshino was living with Shinobu. Before leaving, Yozuru asks Koyomi to give the same information to a certain girl when he meets her, and Karen states that despite Yozuru's strange behavior, she had the look and feel of being a fighter much stronger than her. After leaving Karen at Suruga's, Koyomi meets Mayoi upon returning home and they are approached by a girl introducing herself as Yotsugi Ononoki, asking for the same directions, just like Yozuru had predicted, and much to his surprise Koyomi finds that not only Yotsugi can see Mayoi, but both Yotsugi and Yozuru know about his and his friends' circumstances.

Shinobu asks Koyomi to take her to the donuts shop. Before leaving, he notices that Tsukihi's scar on her chest was healed, and after stripping her naked, finds that all other scars on her body disappeared too. At the shop, Koyomi asks Shinobu if she knew anything about Yotsugi or Yozuru, but much to his surprise, he finds Kaiki sitting on a nearby table and pays him up for information about them. Kaiki reveals that Yozuru and her familiar Yotsugi are supernatural hunters specialized in immortal beings. Wondering if he or Shinobu may be targeted by them, Koyomi returns home just to find both in front of it. When Tsukihi opens the door for them, Yotsugi instantly attacks her, tearing her body apart. A furious Koyomi launches himself at her, but is easily subdued by Yozuru, who shows him that surprisingly, Tsukihi's body is already restored. She also explains that the Tsukihi in front of him is not his true sister but a phoenix assuming her identity. Shinobu threatens to attack the duo, and Yozuru, despite knowing that the vampire has not enough power to stop her, decides to leave, promising to return in the following day to slay Tsukihi, killing both Koyomi and Shinobu too if they try to stop her again.

After learning from Shinobu that Tsukihi is actually a supernatural being that endlessly reincarnates as a human child after dying, Koyomi leaves Karen standing guard at their house's destroyed front door before setting to the place Oshino used to live to confront Yozuru and Yotsugi. To prepare for their clash, Shinobu draws some of Koyomi's blood to recover part of her former strength and upon meeting the two, agrees to fight Yotsugi while her master deals with Yozuru. Yozuru reveals to Koyomi that she, Oshino and Kaiki were friends from college and it was Kaiki who told her about Tsukihi being a phoenix. After viciously hitting Koyomi, Yozuru learns that her partner was easily defeated by Shinobu, and just when she is about to confront the vampire, Koyomi rises again, claiming that he would never give up on his sister, no matter what kind of creature she is. Realizing his determination to protect Tsukihi and that he never fought with the intention to kill her, Yozuru decides to give up and leaves peacefully with her familiar. Koyomi returns home to check on Tsukihi and declares to her that he will soon introduce his girlfriend to his sisters. In the end, Koyomi is seen meeting Hitagi at a beach.