Increased serum levels of C-reactive protein (CRP), a nonspecific indicator of tissue injury, may be valuable in determining the extent of soft-tissue injury. Patients with three types of musculoskeletal injury were included in this study: anterior cruciate ligament tear (n = 11), Achilles tendon tear (n = 7), and intervertebral disc rupture (n = 18). Patients in these three groups and three control groups (n = 37) had serum CRP levels measured immediately after injury and at 48 hours, 1 week, and 2 weeks postinjury. The status of the injury in both patient groups was confirmed through clinical findings, imaging studies, or surgical findings. Mean CRP levels in all three injury groups were highest at 48 hours (anterior cruciate ligament tears [9.2 +/- 2.1 mg/dL], Achilles tendon tears [10.1 +/- 2.2 mg/dL], and acute disc rupture [4.1 +/- 1.0 mg/dL]). In all three groups, CRP levels dropped significantly (P < 0.001) after 1 week and returned to nearly normal levels by 2 weeks. All control patients had normal levels of CRP (< 1.0 mg/dL). In the absence of other causes, an elevation in CRP concentration will aid in determining the severity of acute tissue injury.