The epidemiology of febrile illness etiologies is under-explored in resource-poor settings. Establishing a local repertory of microorganisms circulating in blood of febrile and afebrile people is important for physicians. Blood was collected from 428 febrile and 88 afebrile children in Makokou (Gabon) and analyzed using polymerase chain reaction. spp. were the pathogens, which were most detected in febrile children (69.6%; 298/428) and in afebrile children (31.8%; 28/88) ( < 0.0001). was the most prevalent species in both febrile and afebrile children (66.8% and 27.3%, respectively). No differences were observed between febrile and afebrile children for and (8.2% versus 10.2% and 3.3% versus 3.4%, respectively). Triple infection with , , and was also detected in 1% of febrile children (4/428). Filariasis due to was detected in 10 febrile patients (2.3%), whereas was detected in both febrile and afebrile children (1.4% and 2.3%, respectively). Bacterial DNA was detected in only 4.4% (19/428) of febrile children, including 13 (68.4%) who were coinfected with at least one species. These were (1.6%, 7/428), and (1.2%, 5/428), and (0.9%, 4/428). , spp., spp., , spp., spp., , and spp. were not detected. This study also highlights the over-prescription and the overuse of antibiotics and antimalarials. Overall, malaria remains a major health problem in Makokou. Malaria control measures must be reconsidered in this region.