During intense physical exercise, the cyclo-oxygenase-2 (COX-2) pathway is upregulated which contributes to soreness. The aim of this study was to determine if there was a clinical affect of deracoxib (COX-2 selective antagonist) on dogs engaged in intense rehabilitation following tibial plateau levelling osteotomy for cranial cruciate ligament rupture. Our hypothesis was that dogs receiving deracoxib would demonstrate less lameness, better range-of-motion (ROM), and faster muscle mass recovery than the control dogs. Thirty dogs were randomised to the treatment (deracoxib at 1-2 mg/kg once daily by mouth) or control (no treatment) group. Outcomes including gait analysis, thigh circumference, and goniometry, were measured by one investigator, who was masked to group preoperatively, and at the end of each intense rehabilitation week (3, 5, and 7 weeks postoperatively). The only difference between groups for any outcome measure at any time point was a greater preoperative stifle ROM in the group receiving deracoxib (p = 0.04). This study showed that treatment with deracoxib did not provide better outcomes when dogs were subjected to intense rehabilitation after tibial plateau levelling osteotomy. Each patient should be evaluated individually to determine if administration of deracoxib is appropriate.