A three year old, intact female English springer spaniel was treated for immune-mediated hemolytic anemia by the Cornell Internal Medicine Service. Immune-mediated hemolytic anemia is a result of aben-ant immune cell activation and production of anti-red blood cell antibodies. Red blood cells are destroyed by subsequent phagocytosis (extravascular hemolysis) or direct complement-mediated lysis (intravascular hemolysis). This patient is unique in that the dog had a combination of extravascular and intravascular hemolysis, while most dogs with IMHA have predominately extravascular hemolysis. In addition, although an inherited red blood cell defect would normally be low on the differential diagnostic list for hemolytic anemia, it was an extra consideration in this patient due to the young age and breed. Phosphofructokinase deficiency is an inherited red blood cell enzyme deficiency that has been described in some pedigrees of purebred English springer spaniels and manifests as a hemolytic anemia after strenuous exercise. This case description will focus on the diagnosis of immune-mediated hemolytic anemia and the unique attributes in this patient.