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Shiori's first appearance in the Kanon 2006 anime is in the first episode, where she is seen walking from the hospital with her mother.
However, she doesn't interact with Yuichi until the second episode, where Ayu accidentally makes snow fall on top of her as she's walking home from the store. The next day at school, Yuichi meets Shiori and he asks her what she is doing there. Shiori tells him not to worry since she is a student at the school, but has the day off due to a sickness. When Yuichi asks what the sickness s, Shiori tells him that it is a simple cold, though she has had it for a long time.
During the next few weeks, Yuichi starts to regularly meet with Shiori at school, and Shiori ultimately confesses to having lied to Yuichi all this time about how serious her sickness is, but does not go into much detail about it.
Yuichi later finds out from a meeting with Shiori's older sister Kaori that Shiori may not live past her next birthday, which is rapidly approaching.
A week before Shiori's birthday, she gets permission from her doctor to attend school for a week just like a normal student. Even after getting the chance to go to school for a week, Kaori still avoids Shiori as much as she can, not wanting to have to experience the pain that Shiori's death will bring if she ends up dying. For Shiori's birthday, Yuichi decides to throw her a birthday party the day before her official birthday at a local café and invites several others to join.
While Kaori does not show up at the start of the party, she later shows up which completely changes the mood of the party. Afterwards, Kaori finally decides to accept Shiori as her younger sister which makes Shiori happier than she had been in recent months.
The rest of the night is spent at Shiori's favorite place in town: next to a very large fountain in the park. Shiori then tells him something that she neglected to talk about the day they first met. That day, Shiori was planning to kill herself by slitting her wrists with a box cutter, but after meeting Yuichi and Ayu on her way home from the grocery store, she could not go through with it, and wanted to meet both of them again.
After a kiss between the two, Shiori falls unconscious in Yuichi's arms; in the 2006 anime series, she leaves to get a drink and disappears. After this point, Shiori is taken back to the hospital and Kaori does not come to school during this time.
At the end of the story, Shiori miraculously heals and is no longer in danger of dying. She confesses to Yuichi in tears that she never wanted to die, and that she was only trying to be strong during those difficult times.