While loss of consciousness (LOC) is a key factor in assessing head injuries, its impact on clinical outcomes, including persistent post-concussive symptoms, mental health disorders, quality of life, and neurodegeneration, remains unclear. This systematic review explores the association of LOC in Mild Traumatic Brain Injury (mTBI) with clinical outcomes such as mental health, quality of life, and risk of neurodegenerative diseases. Comprehensive systematic review methodology; two electronic databases (PubMed, Embase) were systematically searched from January 1990 to December 2024. Pooled odds ratios (OR) were obtained using a random effects model. A total of 595 studies were assessed with 30 trials meeting inclusion criteria. The presence of LOC is associated with worsened clinical outcomes including persistent post-concussive symptoms (OR 1.89, 95% CI: 1.59-2.25), post-traumatic stress disorder (OR 1.81, 95% CI: 1.54-2.12), depression (OR 2.69, 95% CI: 2.10-3.43), and overall health-related quality of life (OR 1.84, 95% CI: 1.49-2.26). These findings suggest that the role of LOC in the outcomes of mTBI supports a higher risk of poorer short and long-term outcomes. Future studies may investigate variation in post-mTBI sequelae among those with similar LOC timelines.