The amount of oxidative stress in patients with an isolated traumatic brain injury (ITBI) can be estimated by measuring several biochemical parameters, such as total antioxidants, lipid peroxidation, protein oxidation, and others. Unfortunately, measuring these parameters is time-consuming, impractical in a clinical setting, and may miss important factors contributing to the overall redox balance. Here we suggest that the overall oxidative status in ITBI patients can be assessed by measuring plasma oxidation-reduction potential (ORP). Daily whole blood samples were obtained from severe ITBI patients (abbreviated injury score [AIS] >or=3, n = 32), and demographically similar non-head injury traumatized patients (n = 26) until discharge. Whole blood was also collected from patients with minor to moderate ITBI (AIS <or= 2, n = 18) and healthy volunteers (n = 22). Admission plasma ORP was significantly elevated in all traumatized patients compared to controls. Maximum ORP was detected on day 6 for severe ITBI and non-head injury traumatized patients. However, maximum ORP values were significantly higher (p < 0.05) in the severe ITBI group (+8.5 mV +/- 3.4 SEM) compared to the non-head injury group (-5.2 mV +/- 2.9 SEM). Additionally, a significantly higher oxidation of human serum albumin (HSA) was measured in all trauma patients compared to controls. These results demonstrate the presence of an oxidative environment in the plasma of traumatized patients, specifically in severe ITBI patients. Therefore monitoring ORP is a potentially useful tool for assessing the degree of oxidative stress, inflammation, severity of injury, and potential efficacy of treatment in ITBI patients.