Following knee ligament injury, clinical and experimental investigations usually focus on the injured ligament, and uninjured ligaments of the same joint are largely ignored and presumed to remain unchanged. The purpose of this study was to characterize changes in mRNA levels for a relevant subset of molecules in the uninjured knee ligaments following combined unilateral medial collateral ligament (MCL) and partial anterior cruciate ligament (ACL) transection in sheep. Semiquantitative reverse transcription-polymerase chain reaction was performed for collagen types I, III, and V; matrix metalloproteinase-13 (MMP-13); and tissue inhibitor of metalloproteinase-1 for both injured and uninjured knee ligaments at 6 and 12 weeks after injury. Collagen type I, III, and V mRNA levels were significantly increased in MCL scars at 6 weeks as well as in the uninjured lateral collateral ligament and the anteromedial band of the ACL (AM-ACL). MMP-13 mRNA levels were also elevated in the MCL at 6 and 12 weeks and in the AM-ACL 6 weeks after injury. In contrast, significant changes in the posterior cruciate ligament were not detected at either time point, indicating specificity in the transient alterations. These results suggest that following injury, responses occur in uninjured ligaments that are specific although transient in nature. These responses may be an adaptive attempt to preserve function until the scar tissue can stabilize the mechanical environment following injury.