Mycoplasma pneumoniae is a microbe known to affect numerous organ systems, and in particular, can cause neurological manifestations. We describe an otherwise healthy child who presented with acute onset intractable headache with magnetic resonance imaging (MRI) findings consistent with posterior reversible encephalopathy syndrome (PRES), a neurological manifestation that presents with headache, vision changes, altered mental status, or seizures. Our patient did not have any of the common etiologies for PRES reported but tested positive for acute M. pneumonia infection. The clinical course followed that expected in PRES with rapid resolution of symptoms and MRI findings in subsequent imaging. Literature review shows association between Mycoplasma infection with encephalitis and cerebellitis, but none with PRES in children. Evidence of recent mycoplasma infection in a healthy patient presenting with clinical/radiological findings consistent with PRES, especially in the absence of known predisposing factors, raises the question of M. pneumoniae infection being a trigger for PRES.