This study investigates the metabolomic and immune alterations in long COVID (LC) patients with chronic fatigue syndrome (ME/CFS). The research compared LC patients with chronic fatigue syndrome to age-sex-matched recovered individuals (R), acute COVID-19 patients (A), and SARS-CoV-2 unexposed healthy individuals (HC). The study found significant differences in metabolomic profiles between LC and other groups, with LC patients showing persistent metabolic abnormalities 12 months after the acute infection. These abnormalities included reduced levels of sarcosine and serine, which were inversely correlated with depression, anxiety, and cognitive dysfunction scores. The study also identified elevated levels of pro-inflammatory biomarkers such as IL-1α, IL-6, TNF-α, Flt-1, and sCD14 in LC patients. Additionally, LC patients exhibited a significant reduction in plasma ATP levels compared to R and HC groups. The study suggests that sarcosine and serine supplementation may have therapeutic implications for LC patients. The study also highlights that LC disproportionately affects females, with nearly 70% of LC patients being female. The findings indicate that LC is associated with persistent metabolic and immune alterations, which may contribute to the long-term symptoms of the condition. The study provides a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC. The study also highlights the importance of further research to validate and establish the efficacy of sarcosine and serine supplements for therapeutic purposes in LC patients. The study was conducted on a single-center cohort of 60 PCR-confirmed SARS-CoV-2 infected individuals, including 30 LC patients, 15 recovered individuals, 15 acute hospitalized COVID-19 patients, and 15 healthy controls. The study was approved by the Human Research Ethics Board at the University of Alberta. The study used metabolomic profiling and cytokine and chemokine multiplex analysis to assess the metabolic and immune alterations in LC patients. The study found that LC patients exhibited significant metabolic and immune alterations, which may contribute to the long-term symptoms of the condition. The study also highlights the importance of further research to validate and establish the efficacy of sarcosine and serine supplements for therapeutic purposes in LC patients. The study was supported by grants from the Canadian Institutes of Health Research and the Li Ka Shing Institute of Virology. The study was conducted in accordance with local legislation and institutional requirements. The study was approved by the Ethics Board of the University of Alberta. The study was conducted on a single-center cohort of 60 PCR-confirmed SARS-CoV-2 infected individuals, including 30 LC patients, 15 recovered individuals, 15 acute hospitalized COVID-19 patients, and 15 healthy controls. The study used metabolomic profiling and cytokine and chemokine multiplex analysis to assess the metabolic and immune alterations inThis study investigates the metabolomic and immune alterations in long COVID (LC) patients with chronic fatigue syndrome (ME/CFS). The research compared LC patients with chronic fatigue syndrome to age-sex-matched recovered individuals (R), acute COVID-19 patients (A), and SARS-CoV-2 unexposed healthy individuals (HC). The study found significant differences in metabolomic profiles between LC and other groups, with LC patients showing persistent metabolic abnormalities 12 months after the acute infection. These abnormalities included reduced levels of sarcosine and serine, which were inversely correlated with depression, anxiety, and cognitive dysfunction scores. The study also identified elevated levels of pro-inflammatory biomarkers such as IL-1α, IL-6, TNF-α, Flt-1, and sCD14 in LC patients. Additionally, LC patients exhibited a significant reduction in plasma ATP levels compared to R and HC groups. The study suggests that sarcosine and serine supplementation may have therapeutic implications for LC patients. The study also highlights that LC disproportionately affects females, with nearly 70% of LC patients being female. The findings indicate that LC is associated with persistent metabolic and immune alterations, which may contribute to the long-term symptoms of the condition. The study provides a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC. The study also highlights the importance of further research to validate and establish the efficacy of sarcosine and serine supplements for therapeutic purposes in LC patients. The study was conducted on a single-center cohort of 60 PCR-confirmed SARS-CoV-2 infected individuals, including 30 LC patients, 15 recovered individuals, 15 acute hospitalized COVID-19 patients, and 15 healthy controls. The study was approved by the Human Research Ethics Board at the University of Alberta. The study used metabolomic profiling and cytokine and chemokine multiplex analysis to assess the metabolic and immune alterations in LC patients. The study found that LC patients exhibited significant metabolic and immune alterations, which may contribute to the long-term symptoms of the condition. The study also highlights the importance of further research to validate and establish the efficacy of sarcosine and serine supplements for therapeutic purposes in LC patients. The study was supported by grants from the Canadian Institutes of Health Research and the Li Ka Shing Institute of Virology. The study was conducted in accordance with local legislation and institutional requirements. The study was approved by the Ethics Board of the University of Alberta. The study was conducted on a single-center cohort of 60 PCR-confirmed SARS-CoV-2 infected individuals, including 30 LC patients, 15 recovered individuals, 15 acute hospitalized COVID-19 patients, and 15 healthy controls. The study used metabolomic profiling and cytokine and chemokine multiplex analysis to assess the metabolic and immune alterations in