Immune-mediated hemolytic anemia (IMHA) is a common cause of anemia in dogs. The immune aggression towards erythrocytes can be triggered by many pathological conditions such as infection, inflammatory disease or neoplasia. Upon ruling out any eliciting conditions, a diagnosis of the primary immune-mediated disease can be made. In this particular case of severe anemia (tested positive for circulating antibodies against red blood cells with flow cytometry), vector-borne diseases (which are a common cause of immunopathology in Mediterranean countries) were excluded, leptospirosis was not. This resulted in an unsuccessful immunosuppressive therapy with prednisone, two whole blood transfusions and ultimately death of the patient. Leptospirosis (confirmed positive in two tests, micro-agglutination test for antibodies and PCR for microbial DNA in urine), can mimic a primary IMHA and must be considered in its differential list of causes. A liver involvement, that included elevated serum activity of liver enzymes and increased serum bile acid was observed at the admission and suggested an etiopathogenesis other than a primary IMHA.