Significance The parasite Trypanosoma brucei causes African sleeping sickness. This disease, which lacks effective treatments, affects millions of humans and livestock in sub-Saharan Africa. This paper reveals a mechanism by which the parasite can evade our immune response. Indolepyruvate is a metabolite produced by the parasite and it manipulates the immune cells, called macrophages, preventing them from becoming fully active. The selective advantage for the parasite of excretion of indolepyruvate is possible modulation of host inflammatory responses to prolong host survival, thereby potentiating transmission of the parasite to the tsetse fly vector and ensuring completion of the life cycle. This discovery could lead to new drug targets and better treatments.