Post-viral fatigue syndrome (PVFS) encompasses a range of complex neuroimmune disorders, including myalgic encephalomyelitis (ME/CFS), fibromyalgia (FM), and long COVID, characterized by disabling fatigue, myalgia, joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. Despite the lack of definitive diagnostic criteria and FDA-approved treatments, mitochondrial dysfunction has emerged as a crucial factor in the pathogenesis of these disorders. Mitochondria play a vital role in cellular energy metabolism and are linked to low-grade systemic inflammation in ME/CFS, FM, and long COVID. Coenzyme Q10 (CoQ10) supplementation has shown promise in alleviating symptoms such as fatigue and pain in these conditions. The article reviews the evidence for mitochondrial dysfunction in PVFS and evaluates the effectiveness of CoQ10 supplementation as a novel therapeutic strategy. Studies have demonstrated that CoQ10 can improve mitochondrial function, reduce oxidative stress, and alleviate symptoms in patients with ME/CFS, FM, and long COVID. However, the quality and bioavailability of CoQ10 supplements are critical factors that need to be addressed in future research. The article concludes by highlighting the potential of CoQ10 supplementation as a therapeutic approach for PVFS, with further randomized controlled trials needed to confirm its efficacy.Post-viral fatigue syndrome (PVFS) encompasses a range of complex neuroimmune disorders, including myalgic encephalomyelitis (ME/CFS), fibromyalgia (FM), and long COVID, characterized by disabling fatigue, myalgia, joint pain, cognitive impairments, unrefreshing sleep, autonomic dysfunction, and neuropsychiatric symptoms. Despite the lack of definitive diagnostic criteria and FDA-approved treatments, mitochondrial dysfunction has emerged as a crucial factor in the pathogenesis of these disorders. Mitochondria play a vital role in cellular energy metabolism and are linked to low-grade systemic inflammation in ME/CFS, FM, and long COVID. Coenzyme Q10 (CoQ10) supplementation has shown promise in alleviating symptoms such as fatigue and pain in these conditions. The article reviews the evidence for mitochondrial dysfunction in PVFS and evaluates the effectiveness of CoQ10 supplementation as a novel therapeutic strategy. Studies have demonstrated that CoQ10 can improve mitochondrial function, reduce oxidative stress, and alleviate symptoms in patients with ME/CFS, FM, and long COVID. However, the quality and bioavailability of CoQ10 supplements are critical factors that need to be addressed in future research. The article concludes by highlighting the potential of CoQ10 supplementation as a therapeutic approach for PVFS, with further randomized controlled trials needed to confirm its efficacy.