In the natural sciences an isolated system is a physical system without any external exchange – neither matter nor energy can enter or exit, but can only move around inside. Truly isolated systems cannot exist in nature, other than possibly the universe itself, and they are thus hypothetical concepts only. It obeys in particular the first of the conservation laws: its total energy - mass stays constant.

This can be contrasted with a closed system, which can exchange energy with its surroundings but not matter, and with an open system, which can exchange both matter and energy. The only truly isolated system is the universe as a whole because, for example, there is always gravity between a system with mass, and masses elsewhere. Real systems may behave nearly as an isolated system for finite (possibly very long) times.

The concept of an isolated system can serve as a useful model approximating many real-world situations. It is an acceptable idealization used in constructing mathematical models of certain natural phenomena; e.g., the Sun and planets in our solar system, and the proton and electron in a hydrogen atom are often treated as isolated systems. But from time to time, a hydrogen atom will interact with electromagnetic radiation and go to an excited state.