This study aimed to verify the relationship between changes in thigh muscle‐localized bioelectrical impedance analysis (ML‐BIA) parameters and performance in a multiple‐set exercise. The sample consisted of 30 female university students (22.1 ± 3.2 years). The ML‐BIA parameters, including localized muscle resistance (ML‐R), reactance (ML‐Xc), and phase angle (ML‐AngF), were evaluated using a tetrapolar bioelectric impedance device operating at a frequency of 50 KHz. The multiple sets protocol was performed with an isokinetic dynamometer. For body composition, total and leg lean soft tissue (LST) were evaluated using dual X‐ray absortiometry. Student's t‐test for paired samples was used to compare the ML‐BIA parameters and thigh circumference pre and postexercise. Linear regression analysis was performed to verify the ∆ML‐PhA as a predictor of peak torque for the three sets alone while controlling for total and leg LST. There were differences in the ML‐R (∆ = 0.02 ± 1.45 Ω; p = 0.001; and E.S = 0.19), ML‐Xc (∆ = 2.90 ± 4.12 Ω; p = 0.043; and E.S = 0.36), and thigh circumference (∆ = 0.82 ± 0.60 cm; p < 0.001; and E.S = 0.16) pre‐ and post‐multiple sets. ΔML‐PhA was a predictor of performance in the first set (p = 0.002), regardless of total and leg LST. However, the ΔML‐PhA lost its explanatory power in the other sets (second and third), and the variables that best explained performance were total and leg LST. The ML‐BIA (ML‐R and ML‐Xc) parameters were sensitive and changed after the multiple sets protocol, and the ΔML‐PhA was a predictor of performance in the first set regardless of the total and leg LST.