Pancreatitis is a well-established but unusual complication of thrombotic thrombocytopenic purpura (TTP). It is also an unusual complication of systemic lupus erythematosus (SLE). However, TTP occurring as a consequence of acute pancreatitis in a patient with SLE has never been reported. We report a 24-year-old African American woman with active systemic lupus (SLE) who developed thrombotic thrombocytopenic purpura (TTP) following an episode of acute pancreatitis. The TTP was manifested by low-grade fever, microangiopathic hemolytic anemia, renal insufficiency, altered mental status, seizures and thrombocytopenia. The patient was initially treated with pulse corticosteroids with inadequate response and subsequently with daily plasmaphresis, leading to full remission. This case represents first report of pancreatitis leading to TTP in a patient with systemic lupus erythematosus.