Most traumatic brain injuries (TBIs) that occur every year are classified as ‘mild’. Individuals involved in high-risk activities may sustain multiple mild TBIs. We evaluated the acute physiological and histopathological consequences of mild TBI in a mouse model, comparing sham injury, single impact, or 5 impacts at a 24- or 48-hour inter-injury interval. A single closed skull impact resulted in bilateral gliosis in the hippocampus and entorhinal cortex that was proportional to impact depth. Midline impact, at a depth just above the threshold to induce transient unconsciousness, produced occasional axonal injury and degenerating neurons accompanied by astrogliosis in the entorhinal cortex and cerebellum. Mild TBI repeated every 24 hours resulted in bilateral hemorrhagic lesions in the entorhinal cortex along with significantly increased neurodegeneration and microglial activation despite diminished durations of apnea and unconsciousness with subsequent impacts. Astrogliosis and diffusely distributed axonal injury were also observed bilaterally in the cerebellum and the brainstem. When the interval between mild TBIs was increased to 48 hours, the pathological consequences were comparable to a single TBI. Together, these data suggest that in mice the brain remains at increased risk for damage for 24 hours after mild TBI despite reduced acute physiological responses to subsequent mild impacts.