We report a case of a 46-year-old female living with HIV since 2010 who was originally from Malawi and had settled in the UK in 2001. She was admitted to our hospital with confusion and quickly noted to have a decreased Glasgow Coma Scale of 10/15. Her biochemical parameters showed the presence of elevated liver function tests (LFTs), clotting abnormalities, and her ammonia were found to be >400 mmol/L with a severe metabolic acidosis (pH = 7.05). She was treated for HIV with combined antiretroviral therapy, namely tenofovir disoproxil fumarate, emtricitabine (FTC) and cobicistat boosted atazanavir 2 years previously and had normal LFTs at that time. Her HIV-1 viral load was 1400 copies/ml on admission after recently having an undetectable viral load 2 months previously, and her CD4 count was 480. Her relevant past medical history included insulin-dependent diabetes mellitus. Her other medications included insulin, ramipril, sertraline, amitriptyline, and zopiclone. Toxicology and viral hepatitis screen were negative. Epstein Barr virus (EBV) serology showed evidence of previous exposure, but she was found to have a very high EBV viral load of 55,000 copies/ml, which given her serology, was very likely to be a reactivation of EBV infection rather than a primary EBV infection. In the intensive care unit, the patient deteriorated and died very quickly. The postmortem examination showed extensive hepatic necrosis with collapse. To our knowledge, this is the first case report to show an association between EBV reactivation and fulminant hepatic failure in an individual living with HIV.