Hantavirus pulmonary syndrome (HPS) is an often fatal rodent-borne zoonosis caused by any of at least 20 hantavirus genotypes distributed throughout the Americas. Although HPS has been documented in several bordering countries, it has not been reported in Colombia. Here we report seroconversion to a hantavirus in paired samples from a hospitalized patient with symptoms compatible with HPS from Montería, Córdoba Department, north-western Colombia. Tests for regionally endemic agents including Plasmodium, Leptospira, Salmonella, dengue virus, Brucella, Rickettsia, human immunodeficiency virus and hepatitis viruses were negative. Because the patient was enrolled in a clinical trial for hemorrhagic fevers conducted by the University of Córdoba, serum samples were collected on admission and at discharge. Testing using Sin Nombre virus ELISA showed IgG and IgM seroconversion between samples. The eventual finding of this first clinical case of hantavirus infection in Colombia is consistent with the high prevalence of hantavirus antibodies in humans in the region and the likely exposure of the patient to rodents. The clinical presentation was similar to that found in neighbouring Panama.