This review explores the role of mitochondrial dysfunction in post-viral fatigue syndrome (PVFS), including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and long COVID. Mitochondria, crucial for cellular energy production, have been linked to mitochondrial dysfunction in these conditions, which is associated with low-grade systemic inflammation. The review evaluates the potential of coenzyme Q10 (CoQ10) supplementation as a therapeutic strategy for PVFS, given its role in mitochondrial function and energy metabolism. Mitochondrial dysfunction in PVFS is characterized by impaired ATP production, oxidative stress, and immune dysregulation, contributing to symptoms such as fatigue, pain, and cognitive impairment. Studies have shown that CoQ10 supplementation can improve mitochondrial function, reduce oxidative stress, and alleviate symptoms in patients with ME/CFS, FM, and long COVID. For example, CoQ10 supplementation significantly reduced chronic pain and fatigue in FM patients, and improved symptoms in chronic COVID-19 patients. However, the quality and bioavailability of CoQ10 supplements are critical factors affecting their efficacy. CoQ10 is a lipid-soluble compound with low bioavailability, and its effectiveness depends on the form (ubiquinone vs. ubiquinol) and the manufacturing process. Clinical trials have shown that CoQ10 supplementation can improve mitochondrial function and reduce symptoms in PVFS patients, but more research is needed to confirm its efficacy and safety. The review also discusses the potential of CoQ10 in preventing and treating viral infections by targeting mitochondrial dysfunction. While some studies suggest that CoQ10 may reduce the risk of hospitalization in COVID-19 patients, further research is required to validate these findings. Overall, CoQ10 shows promise as a therapeutic option for PVFS, but its use should be guided by proper formulation and dosing to ensure optimal bioavailability and efficacy.This review explores the role of mitochondrial dysfunction in post-viral fatigue syndrome (PVFS), including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and long COVID. Mitochondria, crucial for cellular energy production, have been linked to mitochondrial dysfunction in these conditions, which is associated with low-grade systemic inflammation. The review evaluates the potential of coenzyme Q10 (CoQ10) supplementation as a therapeutic strategy for PVFS, given its role in mitochondrial function and energy metabolism. Mitochondrial dysfunction in PVFS is characterized by impaired ATP production, oxidative stress, and immune dysregulation, contributing to symptoms such as fatigue, pain, and cognitive impairment. Studies have shown that CoQ10 supplementation can improve mitochondrial function, reduce oxidative stress, and alleviate symptoms in patients with ME/CFS, FM, and long COVID. For example, CoQ10 supplementation significantly reduced chronic pain and fatigue in FM patients, and improved symptoms in chronic COVID-19 patients. However, the quality and bioavailability of CoQ10 supplements are critical factors affecting their efficacy. CoQ10 is a lipid-soluble compound with low bioavailability, and its effectiveness depends on the form (ubiquinone vs. ubiquinol) and the manufacturing process. Clinical trials have shown that CoQ10 supplementation can improve mitochondrial function and reduce symptoms in PVFS patients, but more research is needed to confirm its efficacy and safety. The review also discusses the potential of CoQ10 in preventing and treating viral infections by targeting mitochondrial dysfunction. While some studies suggest that CoQ10 may reduce the risk of hospitalization in COVID-19 patients, further research is required to validate these findings. Overall, CoQ10 shows promise as a therapeutic option for PVFS, but its use should be guided by proper formulation and dosing to ensure optimal bioavailability and efficacy.