Osteoarthritis is a type of arthritis that occurs when the flexible ends of tissues at the end of the bones wear down and it could be due to various causes affecting the daily life of the people. Women are the most important part of society and according to studies it was stated women are more affected than men. There are many biochemical markers involved in the diagnosis of osteoarthritis with other investigations like radiological, and clinical approaches. Here in this study the Cartilage oligomeric matrix protein (COMP) and Tumor necrosis factor – alpha (TNF-?) were determined in post-menopausal knee osteoarthritic female patients and normal healthy subjects taking into consideration of all the exclusion and inclusion criteria. The samples were collected and tests were performed by ELISA. The study suggested that raised levels of the serum COMP & TNF-? in the study group were age-related changes with inflammation and infection at the knee joint which were suggestive of knee osteoarthritis.