AIM: It is well known that head trauma results in damage in hippocampal and cortical areas of the brain and impairs cognitive functions. Theaim of this study is to explore the neuroprotective effect of combination therapy with magnesium sulphate (MgSO4) and progesterone in the7-days-old rat pups subjected to contusion inj ury. mAterIAl and methOds: Progesterone (8 mg/kg) and MgSO4 (150 mg/kg) were injected intraperitoneally immediately after induction oftraumatic brain inj ury. Half of groups were evaluated 24 hours later, the remaining animals 3 weeks after trauma or sham surgery. Anxietylevels were assessed with open field activity and elevated plus maze; learning and memory performance were evaluated with Morris Watermaze in postnatal 27 days.results: Combined therapy with progesterone and magnesium sulfate significantly attenuated trauma-induced neuronal death, increasedbrain VEGF levels and improved spatial memory deficits that appear later in life. Brain VEGF levels were higher in rats that received combinedtherapy compared to rats that received either medication alone. Moreover, rats that received combined therapy had reduced hipocampus andprefrontal cortex apoptosis in the acute period.COnClusIOn: These results demonstrate that combination of drugs with different mechanisms of action may be preferred in the treatmentof head trauma.