Human African Trypanosomiasis (HAT) is an infectious disease due to a protozoa parasite of the Trypanosoma genus. In West and Central Africa, this disease is caused by the subspecies Trypanosoma brucei gambiense. Several foci of this disease are currently active and causing the death of hundreds of people in endemic areas. In this article, we report two cases of gambiense HAT in one Indonesian and one Gabonese men in two historical foci of Gabon in 2019. Both patients had fever with temperatures above 38°C, an altered state of consciousness, cachexia, and multiple dermabrasions on the abdomen related to scratching lesions. The diagnostic revealed second-stage infection of both patients with T. b. gambiense; this result was confirmed by a polymerase chain reaction assay. Despite treatment with a combination of eflornithine and nifurtimox, as recommended by the World Health Organization for late-stage T. b. gambiense HAT, one of the two patients died. Thus, these cases highlight the importance of early HAT diagnosis and prompt patient care to fight effectively against this disease.