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Supplemental Digital Content is Available in the Text.Cornejo-Daza, PJ, Sánchez-Valdepeñas, J, Rodiles-Guerrero, L, Páez-Maldonado, JA, Ara, I, León-Prados, JA, Alegre, LM, Pareja-Blanco, F, and Alcazar, J. Vastus lateralis muscle size is differently associated with the different regions of the squat force-velocity and load-velocity relationships, rate of force development, and physical performance young men. J Strength Cond Res38(3): 450–458, 2024—The influence that regional muscle size and muscle volume may have on different portions of the force-velocity (F-V) and load-velocity (L-V) relationships, explosive force, and muscle function of the lower limbs is poorly understood. This study assessed the association of muscle size with the F-V and L-V relationships, rate of force development (RFD) and maximal isometric force in the squat exercise, and vertical jump performance via countermovement jump (CMJ) height. Forty-nine resistance-trained young men (22.7 ± 3.3 years old) participated in the study. Anatomical cross-sectional area (ACSA) of the vastus lateralis (VLA) muscle was measured using the extended field of view mode in an ultrasound device at 3 different femur lengths (40% [distal], 57.5% [medial], and 75% [proximal]), and muscle volume was estimated considering the VLA muscle insertion points previously published and validated in this study. There were significant associations between all muscle size measures (except distal ACSA) and (a) forces and loads yielded at velocities ranging from 0 to 1.5 m·s−1(r= 0.36–0.74, p< 0.05), (b) velocities exerted at forces and loads ranging between 750–2,000 N and 75–200 kg, respectively (r= 0.31–0.69, p< 0.05), and (c) RFD at 200 and 400 milliseconds (r= 0.35–0.64, p< 0.05). Proximal and distal ACSA and muscle volume were significantly associated with CMJ height (r= 0.32–0.51, p< 0.05). Vastus lateralis muscle size exhibited a greater influence on performance at higher forces or loads and lower velocities and late phases of explosive muscle actions. Additionally, proximal ACSA and muscle volume showed the highest correlation with the muscle function measures.