Brucellosis is a disease that may lead to changes in hematologic parameters such as anemia, neutropenia, and thrombocytopenia; however, thrombotic microangiopathy (TMA) is a rare finding. Severe TMA may be associated with life-threatening hematologic, renal, and neurologic disorders. To prevent this mortality caused by brucellosis, prompt recognition of this complication and prompt therapy are essential. A patient with TMA associated with Brucella melitensis is presented who initially presented with fever, skin purpura, epistaxis, confusion, microangiopathic hemolytic anemia, and thrombocytopenia. TMA was treated with plasmapheresis with cryosupernatant plasma replacement, energetically. A rapid improvement in platelet count, lactate dehydrogenase level, hemolytic anemia, and neurologic symptoms was observed with this treatment. For cases with infection-induced thrombotic microangiopathy, short-term plasmapheresis may be applied as an urgent therapy in addition to antimicrobial therapy.