Background. This report aims to discuss the mechanism of pleural and pericardial effusion related to mifamurtide which is an immunological agent used as adjuvant chemotherapy in osteosarcoma. Case. Mifamurtide (2 mg/m2) and European and American Osteosarcoma Studies (EURAMOS) protocol were used together intravenously after complete surgical resection. No side effects occurred except for fever after the first dose. However, pleural, pericardial effusion, and splenic nodule formation began 11 months after discontinuation of mifamurtide treatment. Pleural biopsy revealed a type 4 hypersensitivity reaction. We treated the patient with 1,5 mg per day colchicine. Pericardial effusion attacks and nodules in the spleen disappeared. The patient had a mild pleural effusion attack which has not yet repeated. Conclusion. Mifamurtide, which activates macrophages, can also activate immunity with a stand by effect and cause a hypersensitivity reaction.