BACKGROUND: Previous studies have estimated joint torques and electromyogram activity associated with the pitching motion. Although previous studies have investigated the influence of extended pitching (fatigue) on kinematic and kinetic parameters, no attempts have been made to quantify the fatigue associated with a pitching performance. PURPOSE: Considering previous investigations on muscle activity during pitching, this study investigated muscle fatigue in upper and lower extremity muscle groups after a pitching performance. STUDY DESIGN: Descriptive laboratory study. METHODS: Thirteen baseball pitchers from 4 universities and 1 independent minor league team were tested before and after 19 games. Pitchers threw an average of 99 pitches during an average of 7 innings. Shoulder, scapular, and lower extremity muscle strengths were assessed using a handheld dynamometer before and after the pitching performances. RESULTS: Baseline strength tests revealed that the pitching arm was 12% weaker (P=.02) in the empty can test (supraspinatus) compared to the contralateral side. Postgame shoulder strength tests revealed selective fatigue of 15% in shoulder flexion (P=.02), 18% fatigue in internal rotation (P=.03), and 11% fatigue in shoulder adduction (P = .01). Minimal fatigue was noted in the empty can test, scapular stabilizers, and hip musculature. CONCLUSIONS: A trend toward significant baseline strength in internal rotation together with significant selective postgame fatigue on internal rotation of the dominant upper extremity indicate that the internal rotators experience a high performance demand during pitching. Weakness in the empty can test on the dominant arm combined with minimal postgame fatigue was surprising given that studies and injury patterns have indicated a high performance demand on the supraspinatus during pitching.