The story of True Tears revolves around the protagonist Tetsuya Mizuno, a third year high school student whose role the player assumes, and his interactions with his schoolmates during the second half of his final year attending Mizuho Academy, in which the main part of the story takes place. Tetsuya meets Yuzuko Sanada, a heroine and a childhood friend whom he nicknamed Yuzu one day on his way to school. Yuzuko actually has a crush on Tetsuya. To her advantage, she is skilled at cooking and homemaking, but has a timid personality. He later also meets Rui Nakane at the pool after running errands for Asumi Akiyam, his cousin who is also the school nurse.Rui is the main heroine in the story, who holds vast knowledge, and is very affectionate towards animals to the extent where her aim is to become a veterinarian. Despite her love toward animals, she has a severe fear of touching cats due to a past incident.