Recent studies suggest a link between exercise-induced rhabdomyolysis and mutations of the ryanodine receptor (RYR1) associated with malignant hyperthermia (MH). We hypothesized that MH susceptible mice (RYR1^Y522S/wt) would exhibit greater anterior crural muscle (TA and EDL muscles) damage and strength deficits following the performance of a single or repeated bouts of eccentric contractions compared to wild-type (WT) mice. Following a single injury bout, RYR1^Y522S/wt mice produced more isometric torque than WT mice immediately, 3 and 7d post-injury. Moreover, EDL muscle isometric specific force deficits were fully recovered for RYR1^Y522S/wt but not WT mice 14d post-injury. The percentage of fibers in TA muscle exhibiting signs of muscle damage 7 and 14d post-injury were at least 3-fold lesser in RYR1^Y522S/wt than WT mice. Uninjured and injured EDL muscle from RYR1^Y522S/wt mice also displayed greater S-glutathionylation of RYR1 than WT mice. During the weekly injury bouts, torque production by RYR1^Y522S/wt mice was fully recovered before the 3^rd and 4^th injury bouts, while torque was still reduced for WT mice. Three days after performing multiple injury bouts there were ~50% less fibers exhibiting signs of muscle damage in RYR1^Y522S/wt than WT TA muscle. These findings indicate that the RYR1^Y522S/wt mutation protects skeletal muscle from exercise-induced muscle injury and do not support a direct association between MH susceptibility and contraction-induced rhabdomyolysis when core temperature is maintained at lower physiological temperatures during exercise.