Strength deficits associated with eccentric contraction-induced muscle injury stem, in part, from excitation-contraction (E-C) uncoupling. FKBP12 is a 12-kD binding protein known to bind to the skeletal muscle sarcoplasmic reticulum Ca²⁺ release channel (ryanodine receptor, RYR1) and plays an important role in E-C coupling. To assess the effects of FKBP12 deficiency on muscle injury and recovery, we measured anterior crural muscle (TA and EDL muscles) strength in skeletal muscle specific FKBP12 deficient and wild type (WT) mice before and after a single bout of 150 eccentric contractions, as well as before and after the performance of six injury bouts. Histological damage of the TA muscle was assessed after injury. Body weight (BW) and peak isometric and eccentric torques were lower in FKBP12 deficient mice compared with WT mice. There were no differences between FKBP12 deficient and WT mice in pre-injury peak isometric and eccentric torques when normalized to BW, and no differences in the relative decreases in eccentric torque with a single or multiple injury bouts. After a single injury bout, FKBP12 deficient mice had less initial strength deficits and recovered faster (especially females) than WT mice despite no differences in the degree of histological damage. After multiple injury bouts, FKBP12 deficient mice recovered muscle strength faster than WT mice and exhibited significantly less histological muscle damage than WT mice. In summary, FKBP12 deficiency results in less initial strength deficits and enhanced recovery from single (especially females) and repeated bouts of injury than WT mice.