Martins, FM, Santagnello, SB, de Oliveira Junior, GN, de Sousa, JdFR, Michelin, MA, Nomelini, RS, Murta, EFC, and Orsatti, FL. Lower-body resistance training reduces interleukin-1β and transforming growth factor-β1 levels and fatigue and increases physical performance in breast cancer survivors. J Strength Cond Res XX(X): 000–000, 2022—This article ascertains whether resistance training (RT) improves inflammatory markers, fatigue (sensations and fatigability), and physical performance in breast cancer survivors (BCS) and investigates whether the changes in the inflammatory markers, fatigue, and physical performance are associated with each other. Volunteers were randomly divided into 2 groups: control group (n = 11) and RT group (n = 11). Resistance training (3 sets of 8–12 repetitions with 80% 1 repetition maximum (1RM) on 4 exercises—leg extension, leg curl, 45° leg press, and calf raise) was performed 3 times a week for 12 weeks. Self-reported fatigue (SRF), fatigability (critical torque [CT] and W prime [W′]), muscle strength, and circulating inflammatory markers were assessed using the Brief Fatigue Inventory, iDXA, 1RM test, protocol of 60 maximal voluntary isometric contractions, and enzyme-linked immunosorbent assay, respectively. Resistance training reduced interleukin (IL)-1β, transforming growth factor (TGF)-β1, and SRF score and increased muscle strength, 6-minute walk test (6MWT), CT, and W′. In the RT group, the changes in SRF were positively associated with the changes in IL-1β. The changes in muscle strength were associated with the changes in CT and W′, and the changes in the 6MWT were associated with the changes in CT, W′, muscle strength, and SRF. Resistance training improved fatigue and physical performance and reduced IL-1β, and TGF-β1 in BCS. Although improvement in fatigability seems to be dependent on the increase in muscle strength, improvement in the sensation of fatigue seems to be dependent on the reduction in IL-1β after RT. Increase in physical performance seems to be dependent on improvement in muscle strength and fatigue.