A growing body of study evidence on Long COVID syndrome reveals that, in addition to respiratory, olfactory, and gustatory disturbances, further main problems are neuro-psychiatric symptoms such as cognitive dysfunction, sleep disorder, and depression, as well as y long-lasting fatigue. However, effective treatment options of fatigue in general are still very rare. In this review, we explore the plausibility and feasibility of high-dose intravenous (iv) vitamin C in Long COVID related fatigue by referring to our recently published review on nine clinical studies with iv vitamin C for treatment of fatigue due to various diseases and by updating it with regard to three presumable key triggers in the pathophysiology of Long COVID: Psycho-social stress, disturbed neurotransmitter metabolism (e.g. excitotoxicity), and development of autoantibodies. It is concluded that high-dose IV vitamin C might be a suitable treatment option also for Long COVID related fatigue due to its well-known antioxidant, anti-inflammatory, endothelial-restoring, and immunomodulatory effects.