Simple SummaryCanine leishmaniosis is a complex infection that ranges from the apparent absence of disease to a severe fatal clinical illness. Numerous epidemiological serosurveys have been carried out in Europe, although these studies often lack assessment of clinical health status. The aim of this study was to evaluate signalment, immunological and parasitological status correlated with clinicopathological findings ofL. infantum-seropositive apparently healthy dogs living in endemic areas of Europe. Routine laboratory tests, endpoint in-house ELISA to quantify the anti-Leishmaniaantibodies, bloodLeishmaniaquantitative PCR (qPCR) and IFN-γ ELISA were performed. Dogs were classified as healthy or sick depending on the results of routine laboratory tests. Seropositive sick dogs presented a worse clinical status that included a higher proportion of medium to high antibody levels and positive qPCR, lower IFN-γ concentration and several clinicopathological findings compared to truly healthy seropositive dogs. In conclusion, further investigation of apparently healthyL. infantum-seropositive dogs is necessary in the clinical setting, as a significant proportion of seropositive dogs that are sick with clinicopathological findings remain undetected if routine laboratory tests are not undertaken. Performing these routine laboratory tests with the combination of a thorough physical examination will improve early disease diagnosis, treatment and prognosis of clinical leishmaniosis.AbstractCanine leishmaniosis caused byLeishmania infantumis a disease with a wide range of clinical manifestations. Epidemiological serosurveys performed in Europe often lack a thorough assessment of clinical health status of studied dogs. The aim of this study was to evaluate signalment, immunological and parasitological status and clinicopathological findings ofL. infantum-seropositive apparently healthy dogs (n = 212) living in endemic areas. Routine laboratory tests, endpoint in-house ELISA to quantify the anti-Leishmaniaantibodies, bloodLeishmaniaqPCR and IFN-γ ELISA were performed. All dogs enrolled wereL. infantum-seropositive and were classified as healthy (n = 105) or sick (n = 107) according to LeishVet guidelines. The sick group presented a higher proportion of medium to high antibody levels and positive qPCR and lower IFN-γ concentration compared to the healthy group. Sick dogs were mostly classified in LeishVet stage IIa. Biochemical alterations (98%) were the most common clinicopathological findings, with fewer urinary tract (46%) and hematological (40%) alterations. Apparently healthyL. infantum-seropositive dogs can be classified between truly healthy dogs and sick dogs with clinicopathological findings. Sick dogs presented medium to high seropositivity and parasitemia and low IFN-γ concentrations, and their most common clinicopathological abnormalities were serum protein alterations followed by proteinuria and lymphopenia.