Background: The safe timing window for surgery during the acute phase of inflammation due to traumatic brain injury (TBI) has not been studied extensively. We aimed to elucidate the relationship between the timing of surgery and changes in perioperative serum levels of inflammatory cytokines and factors associated to optimize TBI management in low-middle-income countries. Methods: A prospective cohort study was conducted among TBI Patients with depressed skull fractures with a GCS>8 operated at different timing from injury and followed up peri-operatively. We collected the clinical-radiological data, as well as pre-and postoperative venous samples from participants; we then did Luminex Assay to quantify the serum levels of pro/anti-inflammatory cytokines using the kits of 96-well human cytokine 27-Plex-Assay (#M500KCAF0Y®) . We performed the analysis with STATA version 17 and R_studio applying both descriptive and inferential methods.