Objective: to evaluate differences in the expression of genes associated with β-oxidation and de novo synthesis of fatty acids (FAs) in the blood of patients with the late stage of knee osteoarthritis (OA) before total knee arthroplasty (TA) depending on the development of postoperative pain (POP) in order to determine the molecular mechanisms responsible for the development of chronic POP. Material and methods. Blood of 50 patients with stage III–IV knee OA complaining of constant pain and joint dysfunction was analyzed prior to TA. The control group consisted of 26 healthy individuals. Pain intensity was assessed using a visual analogue scale (VAS) and the BPI questionnaire. In addition, pain, stiffness and physical functioning were assessed using WOMAC index and the presence of neuropathic pain was assessed using the DN4 and PainDETECT questionnaires. The development of POP was assessed 3 and 6 months after TA. Total RNA isolated from blood was used to determine the expression of ACLY, ACC1, MLYCD, FASN and CPT1A genes by real-time quantitative reverse transcriptase-polymerase chain reaction. Results and discussion. POP ≥ 30 mm by VAS was detected in 17 patients. Before TA, the expression of most of the analyzed genes was significantly increased compared to controls, while the expression of the FASN gene was comparable in patients with OA and healthy individuals. There were no differences in clinical and functional parameters between the groups of patients with and without POP. Before surgery, patients who subsequently developed POP had significantly higher expression of ACLY and CPT1A genes than patients who were satisfied with the results of TA. At the same time, no differences in the expression of ACC1, MLYCD and FASN were found in the groups analyzed. Conclusion. The development of POP is associated with an increased supply of FAs to the mitochondria caused by overexpression of the CPT1A gene, as well as with the accumulation of acetyl-CoA, a product of high expression of the ACLY gene, which can be measured in the blood of OA patients before TA.