"I'm sorry, Mei."

- Misaki Fujioka

Misaki Fujioka (藤岡 美咲, Fujioka Misaki) is Mei Misaki's late twin sister. Early in the anime series, Mei claims that Misaki was her cousin.

More than thirty years ago, Misaki and Mei's mother, Mitsuyo Fujioka, was born with a twin sister named Yukiyo Misaki. They both married, and Mitsuyo became pregnant with twins. These twins were Misaki and Mei. Yukiyo also became pregnant, but she lost her baby, leaving her devastated. At that time, the Fujioka family was experiencing financial problems. Because of this and the fact that Yukiyo was still trying to cope with the loss, Misaki and Mei were separated at birth, and Mei was given to Yukiyo. Even though Kirika didn't allow Mei to see her sister and mother, Misaki and Mei were meeting each other secretly. After this, Misaki needed a kidney transplant. In the manga, Mei said that she wanted to donate one of her kidneys to Misaki, but she could not do so because the rules said that children below 15 years of age were not allowed to. In the end, the donor was their mother, Mitsuyo. The transplant was a success, and Misaki's recovery appeared to be progressing smoothly until late April, when Misaki's condition suddenly took a turn for the worst. Before doctors could do anything to stabilize her condition, Misaki succumbed to complications from the transplant. This information is never revealed in the anime, since in that adaptation, Misaki had leukemia.

In the OVA, Misaki is first seen joking around with a random boy about her doppelganger until Mei arrives. She is fun-loving, cheerful, outgoing, and caring towards Mei. She also states that she likes cute things like the dolls in Studio M, just like Mei, thus making this one of their similarities. Her definition of cute is "A little off base," according to Mei. Misaki told Mei that she found out they were twin sisters before Amane (their grandmother) let it slip, because they looked alike.

Misaki is a short girl with slightly pale skin. She has short brown hair with a small braid on the right side of her face and red eyes. Her appearance is very similar to that of Mei. They also have similar names. Misaki Fujioka's "Misaki" is her given name, while Misaki Mei's "Misaki" is her family name. In the manga, she has black hair and black eyes, similar to Mei. Misaki's height is the same as Mei's at 152cm.

Misaki and Mei typically wear coordinated outfits.

Misaki dies in Episode 1 from the 9th Grade Class 3-3 curse, being "the death of April", the first one who died because of the curse. Mei was delivering a present at the Yomiyama Hospital's morgue, a doll. Mei referred to her as "her other half" during her first meeting with Kōichi Sakakibara and later as her twin sister.

In Episode 11, it is revealed that Misaki attended the same elementary school as Takako Sugiura. Takako remembered a "Misaki," though she was confused and thought the girl was Mei, and not her twin sister. This led Takako to suspect Mei was the other, as when they were younger, she remembered Misaki having both eyes.

Misaki appears in Episode 0 (OVA) and meets Mei in secret. The sisters take a ride on a Ferris wheel, but a bird strikes the glass and causes Misaki to fall out. Mei tried to save her sister, but Misaki realized this would only cause them both to fall and slid her hand out of Mei's, telling her she was sorry. Fortunately, they were much closer to the ground than either girl realized, and both survived the ride. After their near brush with death, the two sisters departed. Shortly thereafter, Misaki collapsed due to a flare-up of her leukemia, possibly aggravated by the stress of nearly dying earlier. In her final moments, Misaki tried in vain to grab her doll.

Misaki is resurrected in the novel as "Misaki Makise", the second extra person of that year, as a direct result of the countermeasures' decision to have two nonexistent students. Her mother, Mitsuyo Fujioka, divorced the unnamed Fujioka father and married a man with the last name Makise two years before the event in the novel takes place. As one of the calamity alterations, Misaki adopted Makise's surname as she was resurrected. Misaki appeared at the strategy session in March 2001 as a frail, sickly girl who volunteered as the second "non-exister" but was turned down as the class decided to draw lots instead. Misaki has been hospitalized since April, the start of the school year, and doesn't attend class. It is revealed in Chapter 16 that Misaki is the second extra person, and she is killed in her sleep by Mei with a stab to the neck.

Misaki and Mei were best friends and often met in secret, and were often found together. They talked to each other a lot, and told each other secrets, bathed together, slept together, and dressed similarly, etc. Mei was very attached to Misaki. In Another 2001, the resurrected Misaki is supposed to be Mei's younger sister.