Abstract Ogrezeanu, DC, López-Bueno, L, Sanchís-Sánchez, E, Carrasco, JJ, Cuenca-Martínez, F, Suso-Martí, L, López-Bueno, R, Cruz-Montecinos, C, Martinez-Valdes, E, Casaña, J, and Calatayud, J. Neuromuscular responses and perceptions of health status and pain-related constructs in end-stage knee osteoarthritis during resistance training with blood flow restriction. J Strength Cond Res XX(X): 000–000, 2023—We aimed to evaluate the neuromuscular responses and their relationship with health status, kinesiophobia, pain catastrophizing, and chronic pain self-efficacy in patients with end-stage knee osteoarthritis during acute resistance training with different levels of blood flow restriction (BFR). Seventeen patients with end-stage knee osteoarthritis participated in 3 experimental sessions separated by 3 days, performing 4 sets of knee extensions with low load and 3 levels of concurrent BFR performed in a random order: control (no BFR), BFR at 40% arterial occlusion pressure (AOP), and BFR at 80% AOP. Normalized root-mean-square (nRMS), nRMS spatial distribution (centroid displacement, modified entropy, and coefficient of variation), and normalized median frequency (nFmed) were calculated from the vastus medialis (VM) and lateralis (VL) using high-density surface electromyography. Subjects were asked to report adverse effects after the sessions. In the VM, nRMS was higher with 80% AOP than with 40% AOP (p = 0.008) and control (p < 0.001), whereas there were no differences between conditions in the VL. Normalized root-mean-square also showed an association with pain catastrophizing, chronic pain self-efficacy, and health status (VM: −0.50, 0.49, −0.42; VL: −0.39, 0.27, −0.33). Spatial distribution varied between conditions but mostly in the VL. Overall, nFmed did not vary, with only a slight increase in the VL with 40% AOP, between set 3 and 4. BFR during knee extensions at 80% AOP increases VM activity and VL amplitude distribution more than 40% AOP and control. Importantly, muscle activity increases are modulated by pain catastrophizing, chronic pain self-efficacy, and health status in these patients, and kinesiophobia seems to especially modulate entropy.