In this study, we examined the effect of four IV fluids (250 mL/kg) on blood glucose and osmolality and brain tissue specific gravity after closed head trauma (CHT) in rats. CHT was delivered at Time 0; blood was sampled at 60 min; fluid infusion began at 75 min and ended at 105 min. Blood was again sampled at 105 and 120 min, and brain tissue specific gravity was determined at 120 min. Five groups (one control and four fluid-treated groups) received CHT, and five other groups (one control and four fluid-treated) did not (n = 9 in each group). 0.45% saline (1/2 NS) and 5% dextrose in water (D5W) accentuated the decrease of brain tissue specific gravity (1.0366 ± 0.0025 and 1.0368 ± 0.0028, respectively; mean ± SD) caused by CHT (1.0395 ± 0.0036), but 5% dextrose in 0.9% saline (D5NS) and 0.9% saline (NS) did not (1.0431 ± 0.0042 and 1.0389 ± 0.0049, respectively). In addition, 1/2 NS decreased blood osmolality (248 ± 6 mOsm/L), D5W increased blood glucose (1095 ± 173 mg/dL), D5NS increased blood osmolality (350 ± 5 mOsm/L) and glucose (1695 ± 76 mg/dL), and NS caused no significant change. We conclude that administering hypoosmolar IV fluids after CHT causes a significant worsening of cerebral edema 2 h after CHT. Implications: We previously reported worse neurological outcome and/or mortality after closed head trauma in rats when 5% dextrose in water or 0.45% saline was given IV compared with 0.9% saline or 5% dextrose in 0.9% saline. The present results and our previous findings indicate that worsening of outcome after closed head trauma in rats may be caused more by edema formation than by hyperglycemia.