Mitochondrial dysfunction is a key factor in long COVID, contributing to persistent symptoms such as chronic fatigue, cognitive disturbances, and exercise intolerance. This review summarizes current evidence linking mitochondrial dysfunction to the pathophysiology of long COVID, highlighting its role in energy production, oxidative stress, immune dysregulation, metabolic disturbances, and endothelial dysfunction. Mitochondrial impairment may result from direct viral effects, immune responses, or autoimmunity, leading to energy deficits and oxidative stress, which exacerbate symptoms. The review also discusses potential therapeutic strategies targeting mitochondrial health, including antioxidants, exercise, dietary modifications, and pharmacological interventions. Long COVID shares similarities with other post-infectious syndromes like ME/CFS, PTLDS, and chronic Q fever, where mitochondrial dysfunction is implicated. Studies have identified mitochondrial abnormalities in long COVID patients, including impaired respiration, altered bioenergetics, and increased oxidative stress markers. Serum peroxiredoxin-3 (PRDX3) is a potential biomarker for mitochondrial dysfunction, showing elevated levels in patients with dizziness but not in those with fatigue. This suggests a nuanced role for PRDX3 in specific symptoms of long COVID. Therapeutic approaches to improve mitochondrial function include antioxidants, NAD+ boosters, and exercise. These interventions aim to alleviate symptoms such as fatigue, cognitive impairment, and muscle weakness. However, further research is needed to develop targeted therapies and understand the mechanisms underlying mitochondrial dysfunction in long COVID. The review emphasizes the importance of a multidisciplinary approach to address the complex nature of long COVID and improve patient outcomes.Mitochondrial dysfunction is a key factor in long COVID, contributing to persistent symptoms such as chronic fatigue, cognitive disturbances, and exercise intolerance. This review summarizes current evidence linking mitochondrial dysfunction to the pathophysiology of long COVID, highlighting its role in energy production, oxidative stress, immune dysregulation, metabolic disturbances, and endothelial dysfunction. Mitochondrial impairment may result from direct viral effects, immune responses, or autoimmunity, leading to energy deficits and oxidative stress, which exacerbate symptoms. The review also discusses potential therapeutic strategies targeting mitochondrial health, including antioxidants, exercise, dietary modifications, and pharmacological interventions. Long COVID shares similarities with other post-infectious syndromes like ME/CFS, PTLDS, and chronic Q fever, where mitochondrial dysfunction is implicated. Studies have identified mitochondrial abnormalities in long COVID patients, including impaired respiration, altered bioenergetics, and increased oxidative stress markers. Serum peroxiredoxin-3 (PRDX3) is a potential biomarker for mitochondrial dysfunction, showing elevated levels in patients with dizziness but not in those with fatigue. This suggests a nuanced role for PRDX3 in specific symptoms of long COVID. Therapeutic approaches to improve mitochondrial function include antioxidants, NAD+ boosters, and exercise. These interventions aim to alleviate symptoms such as fatigue, cognitive impairment, and muscle weakness. However, further research is needed to develop targeted therapies and understand the mechanisms underlying mitochondrial dysfunction in long COVID. The review emphasizes the importance of a multidisciplinary approach to address the complex nature of long COVID and improve patient outcomes.