Approximately 1.4 million people in the United States each year sustain a mild traumatic brain injury (mTBI). Unfortunately, approximately 15% of these patients will have post- concussive symptoms that last longer than three months. Knowledge of the pathophysiological processes underlying susceptibility to poor outcomes is limited, which has impaired the development of effective therapeutics for patients with a mTBI. The present study was designed to assess behavioral and molecular changes post-mTBI in an animal model of genetic susceptibility to poor neurological outcomes, the Kir6.2-knockout mouse. We conducted multiple behavioral tests and analyzed the cellular stress response through assessment of heat shock protein (Hsps) gene expression. We hypothesized that following mTBI, Kir6.2-knockout mice would have increased behavioral deficits, and aberrant Hsp expression. Results from behavioral and molecular analyses demonstrated that outcomes post-mTBI depended on sex and genetic make-up, and that the influence of these factors changed throughout the recovery process.