Celestine is a young and fearless mouse, living at an orphanage. She doesn't believe that bears are dangerous, but one day she is nearly eaten by the starving bear Ernest. This is the beginning of an extraordinary friendship. Eventually, they find themselves being pursued by the police forces of both the mouse and bear cities.

Ernest & Celestine is a charming story based on a children's book series by Gabrielle Vincent, and the animation is reminiscent of A. A. Milne's books about Winnie the Pooh as well as the spectacular animated film universe of Studio Ghibli.