In the North America and Europe, most individuals who develop GBS are adults, although in other parts of the world children are more frequently affected. GBS is not the result of something that the affected individual has done, such as working too hard or becoming stressed. Nor is it the result of failing to do something (exercise, get physical checkups).

Instead, it appears that most cases follow exposure to one of several infectious organisms. The infection often does produce a serious or even noticeable disease in its own right. However, as the immune system develops a specific response to the organism, that response may also "see" and damage parts of the peripheral nervous system that share some molecules in common with the organism. This attack on shared molecules, shared between bacteria or viruses and nerve fibers, has been called "molecular mimicry", and has been suggested as the basis for a number of "postinfectious" autoimmune diseases.

Although this mechanism has not yet been formally proven in GBS, it is very likely to be the basis for the disease. The infectious agents that are best known to precede the Guillain Barre syndrome include infection with a bacteria, called Campylobacter jejuni, that invades the gut and can cause diarrhea, infection with some Herpes viruses including one called Cytomegalovirus, and a few other agents. Rarely the Guillain Barre syndrome appears to follow surgery, childbirth, and other events whose relation to development of the disease are not understood.