AbstractPost-operative neurocognitive disorders are becoming well-documented conditions, with their pathogenesis remaining unclear. Vitamin C is a molecule that has recently demonstrated both a potential link with cognitive function and a significant post-operative decline. Here, we present a case study of a 72-year-old male who underwent total knee replacement surgery. The patient demonstrated a substantial decline in plasma vitamin C concentrations, indicative of a severe deficiency, during the first post-operative week (post-operative Days 3 and 7). Similarly, at these time points, a number of validated paper and pen tests revealed a substantial decline in cognition on tasks relating to total recall, delayed recall, motor speed, recognition and motor speed, with no signs of delirium. These results provide the justification for larger, cohort studies to determine whether post-operative plasma vitamin C depletions could contribute to cognitive deficits post-operatively.