To evaluate whether Chronic Isolated Light-headedness (CIL) commonly manifested in elderly patients is related with cerebral oxygen insufficiency. In this case-control study, 462 patients (aged 40–83 years) with CIL and 238 clinical data matched controls were enrolled consecutively from January 2011 to September 2014. The plasma levels of "phospholipids with solubility similar to that of lysophosphatidic acid" (PSS-LPA), a surrogate marker for cerebral oxygen insufficiency, were assayed for all subjects to compare the occurrence and severity of CIL with the values of PSS-LPA. Patients with CIL had significantly higher plasma levels of PSS-LPA than controls, regardless of having or having not psychogenic abnormalities, χ2 = 448, odds ratio (95% CI) = 140 (72–260), P < 0.001; the mean plasma levels, 0.573 vs. 0.290 mmol/L respectively (P < 0.001). Receiver operator characteristic (ROC) analyses showed plasma PSS-LPA was both sensitive and specific for CIL. The area under ROC curve (AUC) was as high as 0.953 (0.938–0.968). The changes in severity of CIL between two separate assays of one month apart were correlated closely with the changes in plasma levels of PSS-LPA for the same patients, correlation coefficient (Spearman) = 0.90, p < 0.001. CIL is a manifestation of abnormal plasma levels of phospholipids which suggests cerebral oxygen insufficiency. This new finding shows that cerebral oxygen insufficiency is not rare especially in elderly persons. • Chronic isolated lightheadedness (CIL) commonly manifests in elderly adults. • The patients with CIL have strikingly elevated plasma levels of phospholipids • (phospholipids with solubility similar to that of lysophosphatidic acid, PSS-LPA) • The changes in severity of CIL were correlated closely with the changes in plasma levels of PSS-LPA. • CIL is a manifestation of abnormal plasma levels of PSS-LPA which is a surrogate marker for cerebral oxygen insufficiency, [ABSTRACT FROM AUTHOR]