Background: Fast-pitch softball is one of the fastest growing sports, but there is little research regarding pitcher fatigue. Currently, there are no pitch limits or game counts. Questions/Purposes: To study the effect of fatigue on youth fast-pitch softball pitchers during a high school season, we hypothesized increased games pitched during the season would correlate with increased player-reported pain and fatigue and decreased with upper extremity strength and range of motion (ROM). Methods: This prospective crosssectional study evaluated pre-and postgame shoulder and elbow strength, ROM, pain, and fatigue in 17 high school fast-pitch softball pitchers. These measures were recorded at two games, one at the beginning and one at the end of the season. Pitch count and number of games pitched during the season were recorded. We compared pre-and postgame measurements and measurements made at the beginning and end of the season. Results: Supraspinatus, forward flexion strength, and external rotation strength in abduction decreased significantly postgame compared to pregame. Pregame pain and fatigue increased with a greater number of games pitched during the season. Forward flexion, supraspinatus, and external rotation strength decreased with increasing number of games pitched during the season. Conclusions: Fast-pitch softball pitchers experience increased pain and fatigue during a single game and over the entire season. The increase in fatigue may predispose the player to injury. Further studies are needed to understand the relationship of pain and fatigue with predisposition to injury.