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Background: Q fever is a zoonosis caused by Coxiella burnetii which is among the major agents of community-acquired pneumonia in French Guiana. Despite its relatively high incidence, its epidemiology in French Guiana remains unclear, and all previous studies have considered transmission from livestock unlikely, suggesting that a wild reservoir is responsible for transmission., Methods: A country-wide seroprevalence survey of 2697 participants from French Guiana was conducted. Serum samples were tested for phase II IgG antibodies by ELISA and indirect immunofluorescence assays (IFAs). Factors associated with Q fever were investigated, and a serocatalytic model was used to reconstruct the annual force of infection., Findings: The overall weighted seroprevalence was estimated at 9.6% (95% confidence interval (CI): 8.2%-11.0%). The model revealed constant, low-level circulation across French Guiana, particularly affecting middle-aged males (odds ratio (OR): 3.0, 95% credible interval (CrI): 1.7-5.8) and individuals living close to sheep farms (OR: 4, 95% CrI: 1.5-12). The overall annual number of cases was estimated at 579 (95% CrI: 492-670). In the region around Cayenne, the main urban municipality, the high seroprevalence was explained by an outbreak that may have occurred between 1996 and 2003 and that infected 10% (95% CrI: 6.9%-14%) of the population and males and females alike., Interpretation: This study reveals for the first time Q fever dynamics of transmission and the role of domestic livestock in transmission in French Guiana and highlights the urgent need to reinforce Q fever surveillance in livestocks of the entire Guianese territory., Funding: This study was supported by the "European Regional Development Fund" under EPI-ARBO grant agreement (GY0008695), the "Regional Health Agency of French Guiana" and the "National Center of Spatial Studies". The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Competing Interests: The authors declare no competing interest., (© 2022 The Author(s).)