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Visceral leishmaniasis (VL) is endemic in Mediterranean countries. Among immunosuppressed patients, the disease can manifest with atypical clinical features. An unusual clinical manifestation of the disease is fever of unknown origin (FUO). F-18 fluorodeoxyglucose positron emission tomography-computed tomography (F-18 FDG PET) may be useful for detecting inflammatory foci by observing increased metabolism in activated granulocytes and macrophages. We report two cases of PET/CT total body imaging showing a diffuse increase of reticuloendothelial metabolic activity in the spleen and vertebral bodies in two patients diagnosed with VL by direct detection of amastigotes in bone marrow biopsy.