It has been demonstrated that ethanol exerts dose-dependent effects, both beneficial and detrimental, on the outcome of traumatic brain injury (TBI). Recently, it has been reported that co-administration of caffeine (10 mg/kg) and a low amount of alcohol (0.65 g/kg; caffeinol) reduces cortical infarct volume up to 80%, and improves motor coordination, following a rodent model of reversible common carotid/middle cerebral artery occlusion. However, the protective effects of caffeinol following other CNS insults, nor its influence on cognitive function, have been examined. Using a controlled cortical impact model of brain injury, the effect of caffeinol administration on TBI-associated motor and cognitive deficits was assessed. When given 15 min following injury, caffeinol reduced cortical tissue loss and improved working memory. However, no influence on motor skills, Morris water maze performance or associative learning and memory was observed. Delayed administration (6 h post-injury) of caffeinol containing a dose of ethanol (1 g/kg) previously demonstrated to improve motor performance eliminated the working memory benefit and cortical protection. These results indicate that early administration of caffeinol may be beneficial in lessening some of the deficits and cortical tissue loss associated with brain trauma.