Previous studies report that cavum septum pellucidum (CSP) is frequent among athletes with a history of repeated traumatic brain injury (TBI), such as boxers. Few studies of CSP in athletes, however, have assessed detailed features of the septum pellucidum in a case-control fashion. This is important because prevalence of CSP in the general population varies widely (2% to 85%) between studies. Further, rates of CSP among American pro-football players have not been described previously. We sought to characterize MRI features of the septum pellucidum in a series of retired pro-football players with a history of repeated concussive/subconcussive head traumas compared with controls. We retrospectively assessed retired American pro-football players presenting to our memory clinic with cognitive/behavioral symptoms in whom structural MRI was available with slice thickness ≤2 mm (n=17). Each player was matched to a memory clinic control patient with no history of TBI. Scans were interpreted by raters blinded to clinical information and TBI/football history, who measured CSP grade (0-absent, 1-equivocal, 2-mild, 3-moderate, 4-severe) and length according to a standard protocol. Sixteen of 17 (94%) players had a CSP graded ≥2 compared with 3 of 17 (18%) controls. CSP was significantly higher grade (p<0.001) and longer in players than controls (mean length±standard deviation: 10.6 mm±5.4 vs. 1.1 mm±1.3, p<0.001). Among patients presenting to a memory clinic, long high-grade CSP was more frequent in retired pro-football players compared with patients without a history of TBI.