In early March 2013, an outbreak of diarrhea accompanied by acute febrile respiratory syndrome, affecting a community of gold miners working at a single site in the tropical forest, was reported to health authorities by the Maripasoula Remote Prevention and Care Center (French Guiana). Of the 34 patients, 12 with severe clinical symptoms were hospitalized at the Cayenne Hospital and underwent epidemiological, clinical, and microbiological investigation. Based on initial laboratory results and descriptive data collected, the epidemiological investigation suggested the possibility of two overlapping epidemics. The microbiological investigation supported this hypothesis by revealing the co-occurrence of seasonal influenza A/H1N1pdm2009 associated with numerous parasitic, bacterial, or viral co-infections, including 3 cases of Shigella flexneri and 8 cases of hookworm infection. All patients had a favorable clinical course, with rapid recovery following appropriate treatment. The presence of these pathogens and their association reflect the precarious sanitary conditions and high levels of overcrowding in these gold-panning camps. The severity of the clinical presentations was primarily due to co-infections or superinfections. This outbreak highlights the high health needs and risks of this population and the importance of strengthening hygiene measures and targeted prevention strategies.