Viral encephalitis can lead to encephalopathy, epileptic activity, focal neurological deficits, and death. Prompt recognition and a high index of clinical suspicion can lead to early initiation of appropriate management. We describe an interesting case of a 61-year-old presenting with fever and altered mental status, diagnosed with numerous episodes of viral encephalitis caused by divergent and recurrent viruses. On his initial presentation, lumbar puncture revealed lymphocytic pleocytosis and positivity for Human Herpesvirus 6 (HHV-6), and he was treated with ganciclovir. On subsequent admissions, he was diagnosed with recurrent HHV-6 encephalitis as well as Herpes Simplex Virus 1 encephalitis and treated with ganciclovir, foscarnet and acyclovir. Despite prolonged courses of treatment and resolution of symptoms, he continued to have persistently high plasma viral loads of HHV-6, consistent with probable chromosomal integration. In this report, we emphasize the clinical pearl of chromosomally integrated HHV-6 that can present in a patient with persistently high plasma viral loads of HHV-6, that are non-responsive to treatment. Individuals with chromosomally integrated HHV-6 may be more susceptible to other viral infections.