The clinical presentation of chronic fatigue syndrome (CFS) includes cognitive disturbances, debilitating fatigue, widespread pain and flu-like symptoms which limit patients' ability to perform the activities of daily living and, as a consequence, drastically lowering their quality of life. While the underlying causes remain largely unknown, some studies do suggest that CFS might be caused by viral infections and exposure to environmental toxins. This illness is associated with an aberrant activation of immune responses and abnormal mitochondria function. Owing to the key role of lipids in modulating immune and mitochondria function, the current study will attempt to identify lipids associated with these functions as novel blood biomarkers of CFS. Recent studies show abnormal profiles of ω-3 and ω-6 polyunsaturated fatty acids (PUFA) in patients with CFS compared to controls. Levels of long-chain acylcarnitines are decreased in patients with CFS. Furthermore, alteration in ether phospholipid (PL) that are synthesized in peroxisomes were also altered in blood from CFS patients. We therefore hypothesize that lipids associated with modulating immune responses and mitochondria and peroxisome function may be indicative of the underlying biological perturbations of their functions in CFS. In this proposal, we will apply a highly versatile reverse phase capillary based liquid chromatography system coupled to a high resolution and high mass accuracy LTQ Orbitrap mass spectrometer to identify novel blood biomarkers of CFS. In addition, this study will focus on identifying lipid profiles associated with the severity and types of CFS symptoms, particularly focusing on cognitive problems, fatigue and pain. Given that women are at an increased risk of developing CFS, we will examine lipid profiles which may differ between women and men with CFS. We expect that proposed studies will pave the way for future investigations into understanding the role of lipid metabolism in CFS as it relates to immune and mitochondria disturbances observed in ill patients. Availability of lipid biomarkers which give an indication of the underlying pathology and related symptomatology will aid in providing personalized care to CFS patients where the level of care and interventions provided to ill patients is tailored based on the diagnostic classification, symptom profiles and severity of illness.