African sleeping sickness, also called African trypanosomiasis, disease caused by infection with the flagellate protozoan Trypanosoma brucei gambiense or the closely related subspecies T. brucei rhodesiense, transmitted by the tsetse fly (genus Glossina). Sleeping sickness is characterized by two stages of illness. In the first stage, infected persons typically experience fever, headache, muscle and joint pain, and inflammation of the lymph nodes. The second stage, which develops within several weeks (T. brucei rhodesiense) or within one to two years (T. brucei gambiense), is marked by involvement of the brain and spinal cord, accompanied by personality changes, sleep disturbances, and profound lethargy, frequently ending in death when left untreated.

Infections with T. brucei gambiense occur in an area extending from the west coast of Africa eastward to the East African lakes and southward to the Congo River basin. Cases caused by T. brucei rhodesiense are limited to the highlands of central eastern and southern Africa. Several major epidemics of sleeping sickness occurred in the 20th century, but since then the number of new cases reported annually has declined significantly. In 2012 the World Health Organization published a plan targeting the elimination of sleeping sickness as a public health problem by 2020.

Nagana, a form of sleeping sickness that primarily affects cattle and horses, continues to be a major factor preventing the development of cattle farming in parts of tropical Africa where tsetse flies are endemic.