A four year old, spayed female Peke-A-Poo presented to her local veterinarian for a three day history of lethargy and inappetence. On presentation to the referring veterinarian the following abnormalities were detected: a temperature of 105 F, hematocrit of 22%, slide macroagglutination, positive Coombs’ test, spherocytosis, and hyperbilirubinemia. The dog was treated with prednisone, doxycycline, and famotidine. She was referred to Cornell University Hospital for Animals three days into treatment for deterioration in clinical signs and a drop in hematocrit. On presentation to Cornell, the dog was quiet, but alert and responsive. Her mucous membranes were pale and slightly icteric with a capillary refill time of less than 2 seconds. She was tachycardic with a grade I/VI left systolic heart murmur and bounding femoral pulses. An enlarged spleen was detected on abdominal palpation. A complete blood count revealed a severe heterogenous, macrocytic, normochromic, regenerative anemia with the following red blood cell morphology: anisocytosis, howell-jolly bodies, polychromasia, siderocytes, spherocytes, and auto-agglutination. This case report will discuss the diagnostic workup of an anemic patient, differential diagnosis for regenerative anemia, and the clinical features, laboratory test results, treatment, and outcomes of dogs with immune-mediated hemolytic anemia.