Current diagnostic tools to assess neurological injury after aneurysmal subarachnoid hemorrhage (aSAH) and traumatic brain injury (TBI) have poor discriminatory abilities. Free radicals are associated with the pathophysiology of secondary damage after brain trauma. We examined cerebrospinal fluid (CSF) lipid markers of oxidative stress, isofurans (IsoFs), F(4)-neuroprostanes (F(4)-NeuroPs), and F(2)-isoprostanes (F(2)-IsoPs), in two case-controlled studies in patients with aSAH or severe TBI. Patients with aSAH (n=18) or TBI (n=18) were age and gender matched with separate control groups. CSF samples were collected from patients within 24 h of the injury. CSF IsoFs and F(4)-NeuroPs were increased in aSAH patients compared with their controls. In TBI patients, IsoFs and F(4)-NeuroPs were increased compared with their controls. F(2)-IsoPs were increased in aSAH patients, but not in TBI patients, compared with their respective controls. CSF IsoFs and F(4)-NeuroPs are consistently increased after a catastrophic central nervous system injury. These results suggest their measurement may enhance the management of unconscious patients in neurological care.