Objective: To investigate the effects of exercise training alone and in combination with kinesio taping on pain, functionality, and circulating cartilage oligomeric matrix protein (COMP), and matrix metalloproteinase (MMP)-1, and -3 at rest and immediately after walking exercise in knee osteoarthritis (OA). Design: A total of 22 female patients diagnosed with knee OA were randomly divided into the exercise training (ET) or exercise training plus kinesio taping (ET + KT) groups. The patients in the ET performed exercise training for 6 weeks. The patients in the ET + KT group were applied with kinesio tape in addition to the exercise training for 6 weeks. In both groups, 20 minutes of walking exercise were performed before and after the interventions. The pain and functional status of the patients were assessed using visual analogue scale (VAS) and Western Ontario McMasters Osteoarthritis Index (WOMAC) before and after the intervention at rest, respectively. Blood samples were taken at rest and immediately after the walking exercise before and after the interventions for the analysis of COMP, MMP-1, and MMP-3 levels. Results: In both groups, pain and functionality scores were significantly improved after the interventions (P < 0.05). COMP, MMP-1 and MMP-3 levels were higher immediately after walking exercise when compared with rest in both groups before and after the intervention (P < 0.05). Conclusions: Exercise training and exercise training plus kinesio taping improved pain and physical function; however, the COMP, MMP-1, and MMP-3 levels did not change.