Background: Q fever is a zoonotic infectious disease characterized by fever, malaise, chills, significant weakness, and muscle pain. In some cases, the disease can become chronic and affect the inner membranes of the heart, such as the valves, leading to endocarditis and a high risk of death.Coxiella burnetii(C. burnetii) is the primary causative agent of Q fever in humans. This study aims to monitor the presence ofC. burnetiiin ticks collected from small mammals and cattle in the Republic of Guinea (RG). Methods: Rodents were trapped in the Kindia region of RG during 2019–2020, and ticks were collected from cattle in six regions of RG. Total DNA was extracted using a commercial kit (RIBO-prep, InterLabService, Russia) following the manufacturer’s instructions. Real-time PCR amplification was conducted using the kit (AmpliSens Coxiella burnetii-FL, InterLabService, Russia) to detectC. burnetiiDNA. Results and Conclusions: Bacterial DNA was detected in 11 out of 750 (1.4%) small mammals and 695 out of 9620 (7.2%) tick samples. The high number of infected ticks (7.2%) suggests that they are the main transmitters ofC. burnetiiin RG. The DNA was detected in the liver and spleen of a Guinea multimammate mouse,Mastomys erythroleucus. These findings demonstrate thatC. burnetiiis zoonotic in RG, and measures should be taken to monitor the bacteria’s dynamics and tick prevalence in the rodent population.