High-dose intravenous vitamin C (IVC) achieves plasma concentrations that are not attainable by oral administration and has been investigated as an adjunct in sepsis, oncology, and symptom management. To synthesize the evidence regarding the clinical benefits and risks of high-dose IVC, as well as the potential advantages of on-site infusion, a PRISMA-informed search of PubMed/PMC, Scopus, and Web of Science (2010–2025) was conducted, prioritizing randomized controlled trials, systematic reviews, and high-quality observational studies. Pharmacokinetic and mechanistic studies of IVC support plausible physiologic benefits through antioxidant effects, catecholamine biosynthesis, and immune modulation, with recent evidence showing down regulation of pro-inflammatory STAT1/PD-L1 pathways in experimental sepsis. Oncology phase I and II studies demonstrate safety and quality-of-life improvements; a randomized phase II pancreatic trial reported a promising survival benefit when combined with chemotherapy. Some of the major risks include oxalate nephropathy and hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency, especially with very large or repeated doses, suggesting pre-screening to avoid these risks. Furthermore, the literature on home infusion and IV therapies is limited; however, the expanding home infusion infrastructure offers an avenue for monitored IVC delivery. In conclusion, evidence does not support routine use of high-dose IVC in sepsis, and its role in oncology remains supportive and exploratory, with potential risks requiring caution. Furthermore, interest in home-based infusion services is increasing in several healthcare systems, although clinical outcome data specific to high-dose IVC in these settings remain limited.
