In this case report, a 49-year-old man was diagnosed with influenza-associated invasive aspergillosis. Voriconazole therapy was initiated and adjusted to meet therapeutic range. After 16 weeks of treatment the patient was admitted with multifocal, skeletal pains. Alkaline phosphatase was 1,900 U/L and S-voriconazole 9.9 mg/l. A bone scintigraphy and SPECT-CT were performed, and the diagnostic images along with the clinical findings were consistent with voriconazole-induced periostitis. Voriconazole therapy was discontinued, and isavuconazole therapy was initiated, and the patient's symptoms resolved completely.