Thick layers of tissue called fascia separate groups of muscles in the arms and legs from each other. Inside each layer of fascia is a confined space, called a compartment, that includes the muscle tissue, nerves, and blood vessels. (They are surrounded by the fascia much like wires surrounded by insulation.)

Unlike a balloon, fascia do not expand, so any swelling in a compartment will lead to increasing pressure in that compartment, which will compress the muscles, blood vessels, and nerves. If this pressure is high enough, blood flow to the compartment will be blocked, which can lead to permanent injury to the muscle and nerves. If the pressure lasts long enough, the limb may die and need to be amputated.

Swelling leading to compartment syndrome is associated with high-energy trauma, such as from a car accident or crush injury, or surgery. Compartment syndrome may also occur due to tight bandages or casts; with significant swelling, pressure will build up and can cause compartment syndrome. Chronic compartment syndrome can be caused by repetitive activities like running that increase the pressure in a compartment only during that activity.

Compartment syndrome is most common in the lower leg and forearm, although it can also occur in the hand, foot, thigh and upper arm.