Lost in Blue lets you follow a girl and a boy who are stranded on a seemingly uninhabited island. While planning their escape, the two learn survival skills, such as hunting, gathering food, and building tools. You can play the game first as the boy, and then play as the girl for a completely different experience. To survive in this adventure, you'll need to learn how to share responsibilities with your partner.

The story begins with the protagonists riding on ship when a massive storm causes the vessel to sink. In the commotion, Skye manages to get on a liferaft while Keith plunges into the water, at which point he loses consciousness.

Keith wakes up on the beach of the south side of a deserted island. After exploring his surroundings, he finds shelter in a cave. The next day, Keith crosses a nearby river and finds Skye asleep next to her raft, which is apparently undamaged. After she wakes up, Keith and Skye meet for the first time and she tells him that she can't see very well because she has lost her glasses. Keith offers to help her look for her glasses, but accidentally steps on them during the search. With Skye's vision severely impaired, she becomes dependent on Keith to guide her safely around the island. The two return to the cave and make a home.