The aim of the study was to analyze the concentrations of sTNFR1 and sTNFR2 in both plasma and synovial fluid of patients with primary knee osteoarthritis (OA) and to determine their relationship to self-reported pain, stiffness and physical function. Twenty-seven patients with knee OA and 19 healthy subjects were enrolled in the study. The Western Ontario and McMaster University Osteoarthritis Index questionnaire was used to evaluate self-reported physical function, pain and stiffness. The sTNFR1 and sTNFR2 levels in the plasma and synovial fluid were measured by enzyme-linked immunosorbent assay. The sTNFR1 levels in synovial fluid of OA patients (2,587 ± 66.12 pg/mL) were 2.5-fold higher than in corresponding blood samples and were 1.5-fold higher than in the plasma of healthy controls. The plasma sTNFR2 levels in the patients with knee OA were lower than in healthy controls (2,249 ± 126.3 vs. 2,700 ± 126.3 pg/mL, p < 0.05), and sTNFR2 levels in synovial fluid of knee OA patients (2,021 ± 107.0 pg/mL) were lower than in the plasma of healthy controls. Synovial fluid sTNFR1 levels were negatively correlated with pain and physical function self-reported (r s - 0.6785, p < 0.0001 and r s - 0.4194, p = 0.03, respectively). Synovial fluid sTNFR2 levels were negatively correlated with pain and joint stiffness (r s - 0.5433, p = 0.01 and r s - 0.4249, p = 0.02, respectively). The findings of this study demonstrated the presence of soluble receptors for TNF-alpha, particularly sTNFR1, in the synovial fluid of patients with primary knee OA and the relationship of these receptors with clinical parameters.