We report cases of a 39-year-old woman with chronic lymphocytic leukemia and of 21-year-old man with chronic granulomatous disease treated for cerebral aspergillosis. Patients required radical surgery respectively for infection progression despite adequate isavuconazole plasma concentration or neurological complication. We thus decided to measure brain isavuconazole concentration. These results suggest that the concentrations of isavuconazole obtained clearly differ in the infected brain tissue from those obtained in the normal brain tissue and the cerebrospinal fluid.