Background Human Herpes Virus 6 (HHV6) is commonly associated with encephalitis following bone marrow transplantation. However,hippocampal atrophy and global hypometabolism are rare findings in HHV6 encephalitis. Case Report A 41-year-old right-handed woman with acute lymphoblastic leukemia presented with fever and mental changes 2 weeks afterreceiving a sibling bone marrow transplant. The patient’s cerebrospinal fluid (CSF) was positive for HHV-6 deoxyribonucleic acid (DNA),but was negative for other viral DNA. Brain magnetic resonance imaging revealed atrophic changes in bilateral medial temporal lobes. Following4 weeks of ganciclovir therapy, a CSF exam was negative for HHV-6 DNA and the patient’s neurological symptoms partially improved. However, she was disoriented and had severe retrograde and anterograde amnesia. 18F-fluorodeoxyglucose-positron emission tomographyindicated global hypometabolism in the medial temporal lobes and the fronto-parietal cortices. Conclusions This is a rare and unusual case of hippocampal atrophy in the acute stage of HHV6 encephalitis. Our imaging findings mayreflect the chronic indolent course of HHV6 encephalitis.