Mei first meets Kōichi Sakakibara in the hospital's elevator and tells him that she's going to the morgue where her "other half" is waiting for her. She is later seen on the school roof sketching. Kōichi asks many questions, and Mei implies that she hates being questioned. She is seen talking with him many times.
In Episode 3, when Kōichi had finished his test, he went outside after seeing Mei leave the classroom. She tells him that she doesn't exist and that he may be the only one who can see her, leaving him shocked. At that time, Yukari Sakuragi runs out of the classroom, grabs her umbrella, and runs towards Kōichi's direction. However, after seeing Mei, she becomes frightened and runs in the other direction. She trips on the stairs and her neck is skewered by the aforementioned spear-like umbrella.
Kōichi meets her again in the doll store, where she warns him to be careful since "it" has started and disappears mysteriously soon after.
In Episode 5, it is revealed that Mei really exists when Kōichi finds the class roster along with a sheet of paper written "Ask Mei Misaki about it" in it. Kōichi visits the doll store once again, and Mei takes him up to her apartment through an elevator hidden behind a curtain. She asked Kōichi if he suspected her of being a ghost. She assures him she is alive and is positive she has not died. Since "it" has started again, Mei tells him everything about the class curse, the unknown reasons for the deaths, and the prevention measures of the class. Kōichi and Mei's relationship continues to develop to the point that he frequently comes to Mei's apartment, and on one such occasion, he meets Kirika, Mei's mom, who she says treats her like the other dolls in her house. Later on, she tells Kōichi that she will be going on a vacation to her beach house with her parents, so she won't be back for a week. When the others go to find information on the curse from a worker at a hotel by the beach named Katsumi Matsunaga, Kōichi meets Mei there, and they talk about her family. Mei tells him that her father doesn't come to Japan often and that they aren't really close, despite being a family. While they talk, their hands touch as they build a sand castle, a seemingly unimportant part of the story, but a detail that shows how Mei and Kōichi's relationship is progressing.
After it is decided that there should be a contest to see who can catch the most ingredients to make lunch. Mei shows Kōichi a starfish and a pufferfish, but he tells her that they aren't edible until she finds an octopus, which latches onto her. This scares her, and she tells Kōichi to get it off of her. They look at their findings and show them to Reiko, who, after a long deliberation, declares a draw. Matsunaga later finds them, but tells them that he can't remember anything except for someone possibly dying in the mountains on the class trip to the shrine. Suddenly, a strong breeze comes and blows Takako Sugiura's beach ball out far into the ocean. Junta Nakao says he will go get it, swimming out to retrieve the lost plastic item. But when the ball appears just to be within reach, he stops moving, just floating out in the ocean. Kōichi and Matsunaga swim out to save him, only to witness his body being sliced by an oncoming motorboat. Mei stands by Izumi Akazawa on the beach in shock. In Episode 9, Mei is walking along with Kōichi behind Tatsuji Chibiki, who asks them about the behavior of Junta the day he died. Kōichi and the others mention that he was suffering from car sickness and that he was unable to swim straight when retrieving the beach ball. After Chibiki clarifies to them that the reason why Junta died had originated in Yomiyama itself, they leave. Later on, when Kōichi, along with Naoya Teshigawara, enters the art club to search for a clue Matsunaga mentioned, they find Mei painting.
Yūya Mochizuki comes hurriedly into the club room, which prompts her to ask them why they were all there. Finally, the trio answers her, and she tags along with them. They reach the floor of the abandoned 9th-grade classrooms. They reach the class 3 section of the hall and search for the clue Matsunaga had left in 1983. While gossiping with each other, Mei tries to open a window to get fresh air. As a result, a big fragment of glass almost falls on her, but Kōichi pulls her back before she is impaled. Kōichi finds the tape, and the group goes to the AV room to find a tape recorder.
In Episode 10, Mei invites Kōichi into her room at the inn they are staying at during the school trip to the shrine in the mountains to see the graduation photo where Misaki Yomiyama appeared.
Mei tells Kōichi the truth about her and her cousin, Misaki Fujioka, who is actually her twin, and Kirika, who is actually her aunt. She tells Kōichi about how she can see things that should remain unseen, stating that she can distinguish the color of death by uncovering her left eye and determining whether something is alive or dead. She also says that the color of death is different from any color that she has ever seen, stating that it does not belong with colors such as red or blue. Kōichi asks who the dead one is. But right when Mei is about to tell him, Naoya bursts into the room, interrupting them, saying that he has done something terrible.
In Episode 11, Naoya admits to Kōichi and Mei that he thinks he might have killed Tomohiko Kazami by accidentally pushing him off the balcony while they were fighting. Kōichi tells Mei and Naoya to go check and see if he is still alive. When they reach the hall, Kōichi notices something odd about the dining room door and walks toward it. He finds Manabu Maejima, who was badly injured, and discovers that the dining room is on fire with the manager dead inside. They hear Takako scream and go up to her room to rescue her. Takako was gone and later appears with a knife, trying to kill Mei. Kōichi protects her, and Takako flees the scene. She plays the tape over the intercom and tells the students that Mei Misaki is the dead one. This prompts everyone to go on a manhunt to find Mei, forcing Kōichi to protect her. They are pursued by the class, and they tried to escape through the window when Yumi Ogura finds them. Yumi follows Mei and Kōichi out the window. She slashes at Mei, but Kōichi pulls her out of the way; Yumi slips and falls off the windowsill to her death.
In the last episode, Takako appears again with her knife, ready to kill Mei, believing she will free her remaining classmates from the curse. Takako stabs Kōichi and charges towards Mei, attempting to kill her. Mei dodges Takako's attack, causing her to become entangled in loose wiring connected to the ceiling. Takako's violent struggle to free herself causes the wires to pull on a loose support beam, which rips through the wires and pulls Takako up, strangling her to death. Mei watches in shock as Takako hangs right in front of her. Izumi arrives, witnesses the scene, and assumes that Mei had killed Takako, since she was holding her knife. She then snaps and says she's going to kill Mei, prompting Mei to run up the steps as more of the ceiling collapses, separating her from Kōichi and Izumi.
In Episode 12, Kōichi and a few other survivors run out of the burning inn. However, he runs back into the building to search for Mei once he realizes she's missing. He runs up the stairs and discovers that Izumi has cornered Mei on the other side of the floor. As Izumi attempts to kill Mei, Kōichi manages to stop her in time. The entire platform collapses, causing them to fall to the bottom floor. When Izumi finally gets a hold of Mei, she attempts to kill her, but is stopped by Kōichi; right at that moment, lightning strikes. The lightning shatters the hall's giant window, and large glass shards are sent flying towards them. Izumi ends up being skewered against the wall by the glass shards. Shocked, Kōichi runs and removes her from the wall. Mei disappears as Izumi tells Kōichi about her memory of their meeting before she dies.
Kōichi then calls Mei's cell phone, trying to locate her amongst the rubble of the decimated building. She tells him that she is in the backyard and that he shouldn't come, saying that he'll regret it. Kōichi goes to her anyway, ignoring her warning. He finds her with a pickaxe next to a fallen tree and hears sounds coming from underneath. He tries to help the person underneath, only for Mei to stop him. The person struggles under the fallen pile of lumber, and it is revealed to be Ms. Mikami, Kōichi's aunt Reiko. Mei then reveals that Ms. Mikami is the Extra. Kōichi is in disbelief, but Mei explains that she remembers witnessing Ms. Mikami being assaulted and thrown in the river, resulting in her drowning, one and a half years ago. She also points out that their class was the only one to have an Assistant Homeroom teacher and that they actually had the correct number of seats this year, with the missing seat being in the faculty room. Mei's explanation causes him to finally believe her, and he decides to send Reiko back to death himself.
They are later seen at the Mikami family grave together on a sunny, warm day. The grave lists both Ritsuko, Kōichi's mother, and Reiko as deceased. Kōichi and Mei then talk about how they are the only ones to remember Ms. Mikami. They are also the only ones able to see her in the photo they took outside of the inn. Kōichi and Mei walk together, Kōichi asking why she doesn't answer her phone when he calls. Mei tells him that after the incident at the inn, she threw her phone into the river because she hates them. She also mentions that her mother will, without a doubt, get her a new cell phone soon. Kōichi then asks if he may call her sometimes when she gets her new phone. She smiles and replies, "Sure." Kōichi then asks if it is all over, and Mei responds with a reassuring smile.