Mild traumatic brain injury (mTBI) results in a constellation of symptoms commonly referred to as a concussion. It is unclear why certain individuals experience persistent symptoms. Given the growing evidence linking the microbiome with cognition and inflammation, we examined whether longitudinal microbiome patterns were associated with concussion symptoms. A cohort study of 118 children (aged 7-21 years) was conducted. Symptoms were assessed at three timepoints post-injury (4, 11, and 30 days) using the Post-Concussion Symptom Inventory. Saliva microbial activity was measured at each timepoint using RNA sequencing. A linear mixed model assessed the relationship between microbial activity and symptom burden while controlling for age, sex, and days post-mTBI. The participants' mean age was 16 (±3) years. The symptom burden decreased across all three timepoints (25 ± 22, 13 ± 17, and 5 ± 12). The longitudinal symptom burden was associated with elevated activity of