The aim of this study was to investigate the effect of a cyclooxygenase (COX)-2 inhibitor on the recovery of muscle function, inflammation, regeneration after, and adaptation to, unaccustomed eccentric exercise. Thirty-three young males and females participated in a double-blind, placebo-controlled experiment. Seventy unilateral, voluntary, maximal eccentric actions with the elbow flexors were performed twice (bouts 1 and 2) with the same arm, separated by 3 weeks. The test group participants were administered 400 mg/day of celecoxib for 9 days after bout 1. After both bouts 1 and 2, concentric and isometric force-generating capacity was immediately reduced (approximately 40-50%), followed by the later appearance of muscle soreness and increased serum creatine kinase levels. Radiolabelled autologous leukocytes (detected by scintigraphy) and monocytes/macrophages (histology) accumulated in the exercised muscles, simultaneously with increased satellite cell activity. These responses were reduced and recovery was faster after bout 2 than 1, demonstrating a repeated-bout effect. No differences between the celecoxib and placebo groups were detected, except for muscle soreness, which was attenuated by celecoxib. In summary, celecoxib, a COX-2 inhibitor, did not detectably affect recovery of muscle function or markers of inflammation and regeneration after unaccustomed eccentric exercise, nor did the drug influence the repeated-bout effect. However, it alleviated muscle soreness.