Aims: This study was performed to compare the effects of physiological saline and hypertonic saline administered at an early stage in a model of traumatic brain injury associated with hemorrhagic shock. Material and methods: Twenty-eight male Sprague Dawley rats were divided into four groups. The rats in the control group (S) underwent a sham experimental hemorrhagic shock followed by a sham operation. The rats in the trauma group (T) underwent a hemorrhagic shock followed by head trauma and no treatment. The rats in the NS group underwent a hemorrhagic shock followed by head trauma and received 0.9% NaCl. The rats in the HS group underwent a hemorrhagic shock followed by head trauma and received a 7.5% NaCl solution. The weight-drop method was used for achieving head trauma. After the head trauma, hypovolemia was induced by the controlled hemorrhage of 30% of the blood volume. The animals were exposed to hypovolemic shock for a further 30 min prior to fluid resuscitation. Each animal received a single volume infusion of their assigned fluid within few minutes. The effects of different fluids were evaluated after 24-hours by their brain water contents, and histological, and biochemical tests. Results: Group T had a significantly higher mean value for brain water content than did the NS group (P < 0.0001). Also, the HS group had significantly higher mean values for brain water content than the NS group (P = 0.003). Edema and bleeding were more marked in the HS group compared to the NS group (both, P < 0.001) in the histopathological evaluation. Leukocyte accumulation was significantly increased in the untreated rats compared to the HS and NS groups (both, P < 0.001). More red neurons were observed in the rats in the T group than in the NS and HS groups (both, P < 0.001). The mean serum osmolarity was higher in the T group compared to NS, HS, and S groups (all, P < 0.001). The mean plasma ADH levels and the mean plasma aldosterone levels were significantly higher in the T group than in the S, NS, and HS groups (all, P < 0.0001). Conclusion: Although not significantly different in biochemistry, animals treated with HS early in hemorrhagic shock secondary to head injury had more brain water than those the received NS as defined histopathologically. Therefore, in emergency settings, NS should be used safely in the early stage of hemorrhagic shock secondary to head trauma.