Osteoarthritis (OA) is a chronic immune-mediated condition characterized by inflammation of the synovial fluid and infiltration of immune cells. The disease phenotype includes cartilage destruction and erosion of the underlying bone. The synovial fluid is a site where secreted mediators and cytokines from intraarticular tissues may accumulate. We hypothesized that mediators related to cytotoxicity may be relevant to the destruction of cartilage within OA joints. Thus, synovial fluid from 40 patients were tested for the presence of molecules secreted by NK cells and cytotoxic T cells via cytometric bead array. Our results show that only 5 of the 13 mediators tested were detected over 90%, indicating that these mediators may be important in the pathogenesis of OA. 1 of the 5 mediators detected have not been previously detected using the same methods as other cytokines. Our results indicate the predominance of mediators related to direct cytotoxicity within synovial fluid of OA patients.