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Ichigo Momomiya is excited to start high school and fall in love. She is in luck when she meets the popular and good-looking Masaya Aoyama, and she immediately develops a crush on him. When Ichigo learns that Aoyama is passionate about the environment, she seizes the chance to ask him out thanks to some tickets to an exhibition about endangered animals. During their date, Ichigo is struck by a mysterious light and faints. Waking up to the sight of Aoyama, she remains unharmed—but they both must escape from a giant rat-like creature after it injures Aoyama. To save her crush, Ichigo awakens her powers and transforms into a heroine with the skills of a cat. After she defeats the monster, researchers Ryou Shirogane and Keiichiro Akasaka explain that Ichigo was chosen to become a part of the Mew Project: a group of five magical girls whose DNA has been infused with those of certain endangered species. Now, Ichigo must find the rest of her teammates to defeat the Chimera Anima—beings infected by aliens who want to take over the world—before it is too late.

After a successful showdown at Tokyo Tower, the Mew Mew girls enjoy a temporary respite. Now that Ichigo Momomiya and Masaya Aoyama have confessed their feelings to each other, Ichigo is overjoyed to spend time with her new boyfriend. However, their quick break gets interrupted, and soon the girls must battle against the Chimera Anima yet again. When things go awry in the ensuing fight, Ichigo is placed in grave danger. Just when things look most bleak, the mysterious Blue Knight arrives and saves Ichigo, proclaiming that he was born to protect her, before disappearing into thin air. With the fate of the world on their shoulders and the identity of the Blue Knight in question, the Mew Mew girls must strive to create balance between alien-fighting and their personal lives.