Systemic mastocytosis (SM) is a rare clinical condition resulting from a clonal proliferation of abnormal mast cells. The clinical presentation may vary from mild cutaneous manifestations to aggressive systemic symptoms including intermittent episodes of anaphylaxis. We present a case of a 69-year-old male with abrupt and recurrent episodes of anaphylaxis with refractory distributive shock following cardiac surgery with cardiopulmonary bypass. Following a complex postoperative course, a bone marrow biopsy ultimately confirmed the diagnosis. Although rare, SM should be considered in the differential diagnosis of postoperative patients with unexplained and recurrent episodes of distributive shock.