Patients and methods: 76 patients were randomly divided into DEX and P groups; DEX loading dose (0.6-µg/kg) was followed by DEX infusion 0.3-ml and 0.1-ml/kg/h during and for 24-h PO. Blood samples (S1-3) were collected for ELISA estimation of serum levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD). CF was assessed 48-hr, 1-wk, 2-wk, and 4- wk PO using the Mini-Mental State Examination (MMSE). Results: At end of surgery, heart rate (HR) was significantly lower with DEX, while mean arterial pressure (MAP) was significantly lower in all patients with significantly lower MAP measures with DEX. Serum levels of TNF-α, IL-6, and MDA were increased; while SOD levels were decreased with placebo than with DEX infusions. Patients' frequency among CF impairment grades and mean MMSE score showed significant differences in favor of DEX till 4-wk PO. Statistical analyses defined high serum levels of TNF-α and MDA in S3 samples at 24-h as the significant sensitive predictors for low MMSE score at 48-h PO. Conclusion: TBI-induced inflammatory and oxidative stresses impaired CF that were aggravated by surgery. Perioperative DEX infusion ameliorated the inflammatory and oxidative responses to surgery for TBI and significantly improved CF to placebo infusion.