Aim:This study aims to investigate the acute effects of sildenafil citrate in severe head trauma, a leading cause of death, and to compare it with the efficacy of mannitol, which is an osmotically active agent frequently used in clinically treating head trauma. Material and Methods:Twenty-eight Wistar-derived albino strain female rats were randomized into four groups comprising seven rats each. These groups were designated as follows: Group I: sham; Group II: traumatic brain injury (TBI); Group III: TBI + mannitol (20% 1 gr/kg, intraperitoneal); and Group IV: TBI + sildenafil citrate (10 mg/kg, intraperitoneal). Sections prepared following the tissue processing of samples obtained from the right prefrontal cortex and right hippocampal regions of the brains of sacrificed rats were histopathologically evaluated. Fractionator method via the StereoInvestigator software program (MicroBrightField) was used to count the neurons. Pyknotic neuron count and pyknotic/ total neuron count were compared between the groups.Results:In the comparison of Group II and IV, pyknotic neuron count (prefrontal; group II: 116.00±30.50, group IV: 80.00±19.47) and pyknotic/ total neuron count (prefrontal; group II: 0,30±0.08, group IV: 0.21±0.02) were significantly lower in Group IV in both regions (p < 0.05). Similarly, in the comparison of Group II and III, the values in Group III were lower in both regions (p < 0.05). Conclusion:Sildenafil citrate decreases neuronal death in the acute phase and produces similar results with mannitol. Therefore, we believe that sildenafil citrate can be a useful alternative for clinically treating acute TBI.