PURPOSE: This study assessed the levels of soluble tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and matrix metalloproteinase 1 (MMP-1) in the synovial fluid from osteoarthritic knees to determine their role as well as the relationship between these levels and the severity of osteoarthritis (OA). METHODS: Synovial fluid was obtained from 44 knees of 40 patients. The Kellgren-Lawrence (KL) grade was measured using radiograph. The concentration of TWEAK and MMP-1 in the synovial fluid was assessed by enzyme-linked immunosorbent assay. The underlying inflammatory factors (erythrocyte sedimentation rate and C-reactive protein) were also measured. We analyzed the correlation between the factors measured. In addition, the samples were subdivided into three groups according to OA severity using the KL grade, and the differences in TWEAK and MMP-1 levels between groups were analyzed. RESULTS: The TWEAK and MMP-1 levels in the synovial fluid showed a positive correlation with each other. The TWEAK and MMP-1 levels were compared between the three groups according to the KL grade, and the levels showed a significant difference. A post hoc test demonstrated that the group with advanced OA showed a lower concentration of both factors when compared to groups with early OA. CONCLUSION: The concentration of TWEAK and MMP-1 in the synovial fluid were relatively high in the early stage of OA, and the levels decreased as the OA progressed.