In early June 2017, an infectious disease specialist at the Niort Hospital Center (CH) reported to Santé publique France an unusual increase in the number of Q fever cases admitted to his department since early May. The Santé publique France unit in Nouvelle-Aquitaine, in collaboration with the Health Surveillance, Alert, and Management Unit (CVAGS), conducted an investigation to identify the source(s) of contamination in order to propose appropriate control and prevention measures. A case was defined as a person residing in or visiting Niort who, between April 15, 2017, and June 16, 2017, presented with symptoms suggestive of Q fever (reported case) and had serological confirmation by the National Reference Center (CNR) for Rickettsia, Coxiella, and Bartonella (confirmed case). Clinical information was collected from the physician at Niort General Hospital, and an exploratory questionnaire on risk exposures was administered to the cases by telephone. Concurrently, veterinary epidemiological investigations, as well as sampling of animals and the environment, were conducted as part of the Animal Health Epidemiological Surveillance Platform (ESA) on farms in the identified area. In total, 11 cases confirmed by the CNR occurred between April 15 and June 13, with a peak in weeks 16 and 17 (April 17–30). The 11 cases were predominantly residents of Niort and the surrounding area within a 20-km radius (mostly near the entrance to the Marais Poitevin). No common professional or recreational activities among the cases were identified as a source of transmission. The veterinary investigation revealed the circulation of the bacteria in several farms in the area. In conclusion, the epidemiological investigation points to either a common source of contamination (which could not be identified) or multiple sources of contamination during the period of potential spread. Letters and an informational meeting were sent to farmers to inform them of the investigation’s results, raise awareness about the disease, and provide recommendations on manure spreading practices, vaccination, and reporting of abortions.