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Background: One of the most important therapeutic maneuvers in head injury patients is to maintain Intracranial Pressure (ICP) and Cerebral Perfusion Pressure (CPP) within normal levels. Aims: To compare the effects of low dose of thiopental sodium and propofol on reducing ICP and CPP in patients with head injury that scheduled for neurosurgical interventions. Settings and Design: Using a randomized, crossover pilot study, we enrolled patients with head injury that scheduled for neurosurgical interventions admitted to ICU unit of a teaching hospital during 2010 to 2011. Materials and Methods: In this pilot study, patients randomized into two equal groups. The first group received bolus injection of thiopental sodium 2 mg/kg and a maintenance dose of 2 mg/ kg/h and the second group was given a bolus dose of propofol 0.5 mg/kg followed by propofol infusion 20 µg/kg/min. All of patients were given dexamethasone 8 mg at time of catheter insertion. ICP measurement catheter was inserted for each patient and ICP, CPP, SPO2 and MAP were recorded hourly for a period of 6 hours. Results: There was no significant difference in sex and age between the two study groups (p>0.05). The mean ICP, CPP, SPO2 and arterial blood pressure were found to be similar with no significant difference between both groups (p>0.05). Conclusion: Both propofol and thiopental sodium were equally effective in monitoring and maintaining CPP and MAP and eventually an ideal SPO2. .