Physical activity promotes changes in joint loads that could either elicit a catabolic or anabolic response. The serum concentration of Cartilage Oligomeric Matrix Protein (sCOMP) is considered a mechano-sensitive biomarker of articular cartilage break down and N-propeptide of type II collagen (PIIANP), as a proposed biomarker of type II collagen synthesis. No studies have investigated both anabolic and catabolic responses of articular cartilage after loaded and unloaded exercise. Using a repeated measures cross-over design, fifteen healthy adults (age 18- 30 yrs) performed three, 30-minute treadmill walking session under 3 loading conditions: (1) no alteration body weight; (2) 12% increase in the individual’s body weight using a weighted vest; and (3) 12% reduction in the individual’s body weight using the lower body positive pressure technology. Venous blood was collected before, immediately after, and 15 and 30 minutes after exercise in order to investigate cartilage break down (sCOMP) and synthesis (PIIANP). A main time effect revealed sCOMP levels were significantly greater immediately post-exercise as compared to before exercise, 15- and 30-minutes post-exercise. There was a significant condition × time effect for PIIANP, indicating that in the loaded condition, PIIANP concentration values at 15 minutes post exercise were 13.8% greater than right after exercise and 12.9% greater than right before exercise. In summary, exercise stimulus alone was shown to induce a significant increase in sCOMP concentration. However, unloading the body weight by 12% might not be enough to attenuate sCOMP concentrations post-exercise. Therefore, further research is needed to investigate how much of weight change during physical activity is beneficial/detrimental for articular cartilage health.