Persistent post-concussive symptoms (PPCS) endure beyond the usual recovery period after concussion. Although the existence of PPCS is well-documented, its pathophysiology is poorly characterized. Emerging research suggests that aerobic exercise may be a viable intervention for PPCS. However, the biological changes that occur with recovery are not well understood. Neurometabolite alterations have been reported widely in mild traumatic brain injury (mTBI) but are rarely investigated in PPCS specifically. Despite their biological relevance to mTBI, the neurometabolites glutamate, γ-aminobutyric acid (GABA) (primary excitatory and inhibitory neurotransmitters) and glutathione (most abundant antioxidant in the brain) are seldom studied. The scarcity of literature on glutamate, GABA and glutathione in clinical mTBI research is likely due to the technical complexity of measuring these neurometabolites non-invasively. This project used advanced magnetic resonance spectroscopy (MRS) to examine glutamate, GABA and glutathione in PPCS patients and age- and sex-matched controls in the anterior cingulate and sensorimotor cortex. Additionally, changes in these neurometabolites were examined in PPCS patients who completed a sub-symptom threshold aerobic exercise intervention. Compared to controls, glutamate exhibited regional reductions in PPCS. Higher GABA was related to greater incidence of previous mTBI. Furthermore, glutathione was related to symptoms of sleepiness and headache burden. The findings of our aerobic exercise intervention for PPCS indicate that exercise may restore healthy cortical metabolism. While these are early results, they provide compelling evidence for the roles of glutamate, GABA and glutathione in PPCS and during recovery with exercise which can inform best practices and the development of other treatments.