Case summary: A 12-year-old male castrated domestic shorthair cat was evaluated for a 10 month history of weight loss. Thin body condition and a grade II/VI systolic parasternal heart murmur was noted during examination. Moderate-to-severe anemia and intermittent thrombocytopenia were identified on serial complete blood counts. Antibodies against feline immunodeficiency virus (FIV) were detected, but vaccination for FIV occurred previously. Echocardiography revealed biatrial and biventricular enlargement, left ventricular hypertrophy and pericardial effusion. Splenomegaly was present on abdominal ultrasound and cytological evaluation revealed macrophagic infiltration with erythrophagocytosis. Cytological evaluation of the bone marrow revealed similar findings. Histopathology of the spleen confirmed hemophagocytosis with no evidence of malignancy. A presumptive diagnosis of hemophagocytic syndrome was made. PCR testing for FIV on the splenic tissue was negative. The cat was treated with lomustine. Disease progression occurred approximately 6 months after diagnosis and the cat was euthanized. Relevance and novel information: To our knowledge, this is one of the few reports describing the diagnosis of hemophagocytic syndrome in a cat. Published version