First described in HIV-infected patients who recently initiated highly active antiretroviral therapy, the immune reconstitution inflammatory syndrome (IRIS) is best characterized as a collection of inflammatory disorders triggered by rapid resolution of immunosuppression. Treatment of IRIS is a clinical challenge due to the variety of clinical presentations and the presence of multiple pathogens capable of causing the syndrome. Hepatosplenic candidiasis, an uncommon form of invasive Candida species infection, was recently suggested to belong to the spectrum of fungus-related IRIS. We report 2 cases of probable hepatosplenic candidiasis according to the guidelines of the European Organization for Research and Treatment of Cancer and the Mycosis Study Group, occurring in pediatric patients with acute leukemia during rapid neutrophil recovery after cytotoxic chemotherapy. In both cases, abdominal computed tomography scan revealed multiple hepatic micronodules, and liver biopsy showed nonspecific granulomatous lesions. Hepatosplenic candidiasis symptoms (fever, nausea and vomiting, abdominal pain) resolved within 2 days after adjunction of corticosteroid therapy to antifungal treatment. Inflammatory markers and related radiologic abnormalities decreased or disappeared within 1 month. Recovery of neutrophil count in a context of hepatosplenic candidiasis may result in a heightened inflammatory response. Corticosteroid therapy in this setting is associated with prompt resolution of the symptoms.