The psychological response to musculoskeletal injuries has been well documented; however, research on the psychological response to concussion is limited. The Profile of Mood States (POMS) and the State-Trait Anxiety Inventory (STAI) have recently been used to assess the psychological recovery of concussions (CONC). Although some studies indicate that psychological response is different for musculoskeletal injuries and concussion, there is currently not enough information to indicate this difference occurs at specific clinical milestones. The purpose of this study was to compare the psychological responses of student-athletes who have been diagnosed with a concussion to those of athletes diagnosed with musculoskeletal injuries with similar recovery duration. Fifteen collegiate athletes who sustained a musculoskeletal injury were recruited and matched with 15 previously collected concussion participants. The main outcome measures were the scores of POMS constructs: tension-anxiety, anger-hostility, fatigue-inertia, depression-dejection, vigor-activity, confusion-bewilderment, and total mood disturbance and STAI (state anxiety only). Two-way MANOVAs were run to determine the effects of group and time on POMS and STAI constructs. There were no significant interactions identified, but follow-up ANOVAs identified a main effect for time for most POMS subscales, with POMS scores improving over time in both groups. Analyses also revealed that tension-anxiety, vigor-activity and the STAI were not affected by time or group. The findings of this study that both groups’ psychological response to injury improves over time and at similar clinical milestones suggests reduction in sports and team-related activities may play a substantial role in the psychological response to either concussion or musculoskeletal injury.