Objective: To assess brain perfusion, gray matter structure, and cognitive performance after one season of high school football. Method: Subjects consisted of 13 high school football players age 15 to 17 (M = 16.7; SD = 0.88) who completed neuropsychological assessments and MRI scans before the start of the season (T1), post season (T2), and three months after post season (T3). Verbal and visual memory, processing speed, verbal fluency, and working memory were assessed using standard measures. MRI included pseudo continuous arterial spin labeling (pCASL) to measure regional cerebral blood flow (CBF) and high resolution T1-weighted structural 3T MRI. A general statistical model was applied to test variability of neuropsychological measures and MRI data across T1, T2 and T3. Two orthogonal polynomial contrasts were examined in a repeated-measure analysis: Linear (change from T1 to T3) and Quadratic (change from T1 to T2 and then T3). Results: Participants showed significantly higher working memory (p = .012), processing speed (p = .017) and verbal fluency (p = .004) from T1 to T3 or linearly. Visual memory showed improvement at T2 but reduced at T3 or quadratic effect. Whole brain blood flow reduced significantly from 63.9 ml/min/100g at T1 to 59.4 ml/min/100g at T3 (Linear: p = 0.04). Regionally, participants showed lower CBF in the left inferior parietal cortex at post-season (T2) and follow-up (T3) compared to pre-season (p < 0.01 [FWE corrected] and K ≥ 164). Additionally, gray matter density of the inferior parietal cortex reduced by1.35% at T2 and remained at T3 (Linear: p = .04). Conclusion: High school football players showed practice effects on working memory, processing speed, verbal fluency and visual memory; however, brain perfusion and gray matter density decreased in left inferior parietal cortex. The left inferior parietal cortex is a key node of the central executive network, and while findings may suggest abnormal physiological and structural changes in these young football players, these differences were not associated with negative cognitive effects. Thus, the clinical implications remain unclear.