[1] At the start of a new game, three colonists (referred to as duplicants) find themselves in an asteroid with isolated pockets of breathable atmosphere, with no memory of how they got there.

The player is tasked with managing and taking care of these duplicants as they try to survive and create a sustainable makeshift space colony.

To help establish the colony, the player directs the duplicants to perform certain tasks, such as mining for resources, growing food, crafting equipment, researching new technologies, and maintaining their own health through nourishment, rest, and hygiene.

[7] Klei's Johann Seidenz said that games such as Dwarf Fortress, Prison Architect, and The Sims influenced the design of Oxygen Not Included.

[8] Nate Crowley, writing for Rock Paper Shotgun praised the game's design and progression, but questioned the ever-growing complexity as a deterrent to more casual gamers, especially those without backgrounds in science and engineering.

[11] GameCentral also gave the game positive reviews, with a total 8/10, praising the scientific accuracy as well as the design, but raising concerns about the difficulty, especially with the lack of in-game learning tools.