Nitric oxide has a definitive role in the complex pathophysiology of traumatc brain injury (TBI). This prospective cohort study investigated the changes in nitric oxide metabolite (NOx) levels in cerebrospinal fluid (CSF) and their correlation with factors associated with severity and prognosis after severe TBI. NOx levels were measured in CSF obtained via ventriculostomy in 44 adult patients admitted after severe TBI (Glasgow Coma Scale ≤ 8/15). The overall mean level of CSF NOx in the study population was 7.40 ± 1.59 μmol/L. Levels of CSF NOx were found to be significantly higher in subgroups of patients with poorer outcome measured by Glasgow Outcome Scale score (p < 0.042), in patients with high intracranial pressure (ICP) readings (p < 0.027) and in those with higher Marshall computed tomography (CT) grading scores (p < 0.026). Simple logistic regression demonstrated that CSF NOx levels were a significant predictor of ICP (b = 0.493, 95%CI: 1.03, 2.58, p = 0.033). A patient with 1 μmol/L increase in NOx level had 1.6 times the odds to have an ICP ≥ 20 mmHg when other confounders were not adjusted. NOx level is also a significant predictor of Marshall CT grading (b = 0.473, 95%CI: 1.02, 2.50, p = 0.037). A patient with 1 μmol/L increase in NOx level had 1.6 times the odds to have a high Marshall grade when other confounders were not adjusted. It can be concluded that CSF NOx levels may serve as a potentially useful biomarker in severe TBI given its significant association with ICP readings as well as Marshall CT grading.