The aim of this study was to explore the relationship between the protein S100B level, cognitive dysfunction, and Glasgow Outcome Scale (GOS) in moderate traumatic brain injury patients. Thirty patients suffering from head injuries undergoing neurosurgery in Dr. Hasan Sadikin General Hospital Bandung, Indonesia, and who were considered eligible based on the inclusion and exclusion criteria participated in this double-blind experimental Randomized Controlled Trial (RCT). The treatment groups (COX-2) were assigned as COX2-I, COX2II, and COX3-IV, six patients in each group. The treatment group was given another dose of sCOX-2 inhibitor 12 hours, 12 and 24 hours after the first dose, and 12, 24 and 36 hours after pre-induction sCOP-2 inhibitor was administered. The GOS score was obtained during the before the surgery and 1 month, 1.5 months, and 2 months postoperative days. The MMSE was performed preoperatively and then on the first to seventh day after the surgery. The results showed that there was a significant decrease in the protein level in all treatment groups including the control group, where the resulting p-value was less than 0.05. Moreover, the treatment group showed a faster time in reaching GOS 5 or be discharged from the hospital compared to the control. In conclusion, it has been demonstrated that the provision of 3 or 4 times of the sCox-2 inhibitor leads to the achievement of a score of 5, while the recovery of the cognitive dysfunction into the normal level is obtained when the SCox2 inhibitor is given 4 times.