Thrombotic thrombocytopenic purpura (TTP) is a serious disorder with a significant morbidity and mortality. Majority of cases of TTP are idiopathic, but some cases may be secondary to connective tissue diseases. TTP has been rarely associated with systemic lupus erythematosus (SLE) and may be refractory to treatment with plasma exchange, requiring immunosuppressive therapy. We describe a patient with TTP and SLE who was refractory to plasma exchange and corticosteroids but responded to anti-CD20 antibody rituximab with continued remission after eight months of follow-up. Rituximab appears to be an effective treatment in refractory cases of TTP associated with SLE.