Proper monitoring of fatigue and muscular damage may be used to decrease the high levels of cardiovascular disease, overuse musculoskeletal injuries, and workers compensation claims within the profession of firefighting. The purpose of this study was to examine muscle damage, muscular fatigue, and inflammation responses following a typical firefighting shift. Twenty-four professional firefighters completed two Physical Ability Tests to standardize the tasks typically performed in a day of work, and to elicit similar physiological responses. Participants were then monitored for 48 h. Prior to, and 48 h following the Physical Ability Tests, participants were evaluated for changes in strength, power, range-of-motion, as well as blood markers including myoglobin and c-reactive protein. Following the Physical Ability Tests, significant differences in myoglobin (p < 0.05), grip strength (p < 0.05), vertical jump (p < 0.05), and sit-and-reach (p < 0.05) were observed. No difference in c-reactive protein was observed (p > 0.05). After 24 hours following a shift, firefighters exhibited decreased strength, power, and range-of-motion. This may lead to decreases in performance and an increased risk of injury.