Non-steroidal anti-inflammatory drugs play a major role in the management of osteoarthritis (OA). However, it remains unknown whether these drugs affect cartilage and synovial metabolism in osteoarthritic joints. The aim of this study was to evaluate the effects of a selective cyclooxygenase (COX)-2 inhibitor, celecoxib, on synovial fluids and tissues in severely osteoarthritic knees. Patients were randomized into three groups and medicated twoweeks prior to total knee arthroplasty with celecoxib, diclofenac sodium, or no medication (control). We checked for the presence of matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and hyaluronic acid (HA) in the synovial fluids of all three groups. MMP-3 significantly decreased in the celecoxib-treated patients (p=0.0031). On the other hand, there were no significant differences among the three groups in their TNF-α and IL-1β levels. HA in the joint fluid was significantly increased in the diclofenac-treated group, while HA was not changed in the celecoxib-treated patients. Our study suggests that celecoxib did not affect the level of HA in the joint fluid in the knee in severe OA, in contrast to the effect of the dual COX inhibitor.