Mild traumatic brain injury (mTBI), especially when it is repeated (rmTBI), can lead to progressive degenerative diseases and lasting neuropsychiatric abnormalities. To better understand the long-term pathobiological changes in mTBI and rmTBI, we exposed rats to single or repeated (5 total; administered on consecutive days) mild blast overpressure, monitored changes in physiological parameters, and determined the plasma levels of select biomarkers at 42 days post injury by proteomics. We unexpectedly found comparable changes in arterial oxygen saturation levels and heart rates of single-injured (SI) and multiple-injured (MI) rats throughout the observation period. Our analyses indicated lasting oxidative stress, vascular abnormalities, and neuronal and glial cell loss in both injured groups. However, MI rats exhibited a relatively more pronounced increase in the plasma levels of most of the tested markers-particularly those associated with inflammation-albeit the differences between the two injured groups were not statistically significant. Our findings indicate that the frequency of blast exposures is an important determinant of the resulting cumulative damage in rmTBI.