Quality cardiopulmonary resuscitation (CPR) is an essential component in cardiac arrest survival. Research indicates that a first responder’s performance is generally inadequate due to many factors including fatigue or distractions. One factor that has not been studied is prior musculoskeletal injuries. This study aims to determine if a correlation exists between firefighter’s CPR performance, fatigue, and prior musculoskeletal injuries. Twenty-nine urban firefighters participated. Researchers were supplied with basic demographics and a self-reported musculoskeletal injury history through secondary injury questionnaires. Participants performed five rounds of single-rescuer CPR followed by a graded exercise test (GXT), then another set of five rounds of CPR. Results indicated that BMI was a predictor for overall CPR score pre-GXT, and BMI and back pain were indicators for full chest recoil percentage pre-GXT. We conclude that an increased BMI may positively impact CPR performance, and the presence of back pain may have a negative impact on performance.