['To examine whether acute inflammation profiles predict posttraumatic depression (PTD) risk 6 and 12 months after traumatic brain injury.', 'University-affiliated level 1 trauma center and community.', 'Adults with moderate to severe traumatic brain injury (acute serum levels: n = 50; acute cerebrospinal fluid (CSF) levels: n = 41).', 'Prospective cohort study.', 'Patient Health Questionnaire; inflammatory biomarkers (interleukin [IL]-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, tumor necrosis factor α, soluble vascular adhesion molecule [sVCAM-1], soluble intracellular adhesion molecule [sICAM-1], soluble Fas [sFAS]).', 'Higher levels of acute CSF cytokine surface markers (sVCAM-1, sICAM-1, and sFAS) in an inflammatory biomarker risk (IBR) score were associated with a 3.920-fold increase in the odds of developing PTD at 6 months (95% confidence interval: 1.163-8.672). Having sICAM-1, sVCAM-1, or sFAS above the 75th percentile had a positive predictive value of 85.7% for PTD risk at 6 months. An IBR score including inflammatory biomarkers IL-7 and IL-8 showed a trending association with 12-month PTD risk (odds ratio = 3.166, 95% confidence interval: 0.936-10.708).'] Do acute inflammatory biomarker profiles predict depression risk following moderate to severe traumatic brain injury?