The pain of CTS is caused by compression of the median nerve that travels through the carpal tunnel. Several conditions are caused by compression of peripheral nerves (such as sciatica) but CTS is the most common of these so-called compressive or entrapment neuropathies.

Compression of the median nerve can have several possible causes. Anything that reduces the amount of space in the carpal tunnel can cause CTS. The disorder is likely caused by a combination of factors. CTS tends to run in families. It is likely that people who have a tendency to develop CTS have congenitally narrow carpal tunnels in their wrists, making it much easier for the nerve to be compressed. Another major factor in the development of CTS is swelling or thickening of the tendons that travel through the carpal tunnel. Some of the other factors that may contribute to CTS include:

• trauma or injury to the wrist (such as sprain or fracture)
• over-activity of the pituitary gland
• under-activity of the thyroid gland (hypothyroidism)
• rheumatoid arthritis
• mechanical problems in the wrist joint
• work stress
• repeated use of vibrating hand tools
• fluid retention such as occurs during pregnancy or menopause
• development of a cyst or tumor in the canal

In many cases of CTS, no obvious cause can be identified.

While many people associate CTS with jobs that require lots of typing on a keyboard, there is little clinical evidence to either support or refute the idea that computer use can cause CTS. However, it does appear that increased hand use or activity can be a major factor in developing carpal tunnel symptoms. Working on an assembly line or another job that requires the same motion to be repeated over a very long period of time seems to increase the risk of CTS. Repeated motions can also result in such repetitive stress disorders as bursitis and tendonitis, which are caused by inflammation of tendons or their protective coverings.