The destruction of the myelin sheath that coats nerves inhibits impulse conduction within the cell and thus decreases its ability to communicate with other cells. The most common cause of central pontine myelinolysis is a rapid, drastic change in sodium levels in the body. Most commonly, this occurs when someone is being treated for low levels of sodium (hyponatremia) and the levels rise too fast, but it can occasionally occur when high levels of sodium in the body (hypernatremia) are corrected too quickly.

This condition does not occur spontaneously; it is a complication of either treatment for other conditions or the other conditions themselves.

Risks include hyponatremia from any cause. Alcoholism, Wernicke-Korsakoff syndrome, and general ill health and malnutrition associated with serious illnesses (cachexia) increase the risk of central pontine myelinolysis.