Background <p>Lean body mass is crucial for maintaining muscle strength, particularly in patients with knee osteoarthritis. While it provides a protective effect against knee pain and functional decline, the specific relationship between total and regional lean body mass and knee pain and function in these patients remains unclear. This study aimed to investigate the relationship between total and regional lean body mass, and knee pain and function in patients with knee osteoarthritis, with subgroup analyses conducted based on BMI and sex.</p> Methods <p>A total of 337 patients were included in the analyses. Clinical information and participant demographics were described descriptively. Linear regression analyses were conducted to investigate the relationship between total and regional lean body mass, and knee pain and function in patients with knee osteoarthritis, with subgroup analyses performed based on BMI and sex.</p> Results <p>The average age of 337 subjects was 63.8 ± 8.1 years, with 260 women (77.2%). Based on BMI, 279 subjects were classified as overweight or obese, and 58 were classified as having normal weight. In subjects who were overweight or obese, a weak negative correlation was found between trunk lean body mass and self-reported knee function decline (β = -0.28, 95% CI: -1.81, -0.15), and knee pain (β = -0.28, 95% CI: -0.58, -0.04). This negative association was more pronounced in male subjects who were overweight or obese (self-reported decreased knee function (β = -0.75, 95% CI: -4.95, -1.50) and knee pain (β = -0.64, 95% CI: -1.43, -0.32)).</p> Conclusion <p>Trunk lean body mass had the largest positively association with improved self-reported knee function and reduced knee pain compared with other regions, which was most pronounced in male subjects with overweight or obese.</p> Trial registration <p>Not applicable.</p>