ABSTRACT. Coxiella burnetii is an underreported zoonotic pathogen in many rural regions globally. We investigated C. burnetii exposure in a remote indigenous tribe residing in the Sierra Nevada de Santa Marta, Colombia. The high seroprevalence of 35% (95% CI, 27–43%) demonstrates the need for One Health studies to identify risk factors, clinical impact, and potential medical, veterinary, and environmental interventions.