Background: Creactive protein has been known as a highly sensitive but non-specific marker for acute inflammation. The pattern of CRP response in trauma patients has not been evaluated in our environment. Aim: The aim of the study was to determine the serial serum level of high sensitivity Creactive protein (hsCRP) in patients with trauma. Methods: This is a longitudinal study conducted at the University of Benin Teaching Hospital, Benin City, Nigeria. One hundred and twenty patients with traumatic injuries were recruited at the accident and emergency unit of UBTH and 30 apparently healthy individuals as controls. A structured questionnaire was administered to all subjects to obtain demographics, injury type, tissue involvement and interventions. Samples were collected from participants for estimation of h-sCRP on days 1, 3, and 8. hsCRP was analyzed using an ELISA method. Results were analyzed with SPSS 16. P value was set at 0.05. Results: A total of 116 patients and 30 controls completed the study. The most frequent cause of trauma amongst the patients was vehicular crashes 80 (69.0%) followed by gunshot injuries 19 (16.4%). The mean serum h-sCRP of the patients on the first day was (166.7 ± 105.3mg/L) but it peaked on the third day post trauma (373.4 ± 131.2mg/L) and declined on the eighth day to 300.0 ± 156.5mg/L) (P = <0.001). Conclusion: Creactive protein levels increase in the blood of trauma patients as a result of tissue damage but decreased after the third day following trauma. However, in the presence of infection, the increase was sustained. We therefore recommend that serial quantitative C-reactive protein measurements be done as an adjunct to surgical care in patients with acute injuries.