We describe the case of a 6-year-old girl with typical infectious mononucleosis syndrome complicated by clustered right hemiconvulsions and disturbed consciousness. Diffusion-weighted magnetic resonance imaging on admission demonstrated reduced diffusion in the left temporo-posterior cortex and pulvinar of the ipsilateral thalamus. Her neurological symptoms resolved completely by the next day, with complete disappearance of abnormal signal intensities on magnetic resonance imaging (MRI). Elevated cerebrospinal fluid interleukin (IL)-6 with normal IL-10 might indicate a neuroprotective role of IL-6 rather than injury. We concluded that the MRI abnormalities could have been due to the seizure activity itself rather than Epstein–Barr virus-associated encephalitis. The recognition of transient seizure-related MRI abnormalities may help in the diagnostic approach to MRI changes in suspected encephalopathy.