In recent years, repetitive traumatic brain injuries have been linked to the progressive neurodegenerative disorder termed chronic traumatic encephalopathy. However, the mechanical characteristics of brain tissue exposed to repetitive loading still lack understanding. This research evaluated the response of porcine brain tissue undergoing cyclic, compressive loading in reference to three impact parameters: cycle number (N25, N50, N100, N150, and N200), strain level (15, 30, and 40%), and strain rate (0.00625, 0.025, 0.10, and 1.0/s). Following mechanical testing, tissue samples were processed for hematoxylin and eosin (H&E) staining. Stress values, hysteresis energy, and decreases in hysteresis energy for all parameters were compared. The data suggest that microstructural brain tissue damage is highly dependent on strain level and cycle number, whereas strain rate did not appear to cause permanent damage in the quasi-static range applied. The onset of permanent microstructural tissue damage may relate to movement of fluid molecules within the tissue.