Purpose: To evaluate anthropometric measures and serum markers of myostatin-pathway activity after different weight-reduction protocols in wrestlers. Methods: Subjects were randomly assigned to a gradual-weight-reduction (GWR) or rapid-weight-reduction (RWR) group. Food logs were collected for the duration of the study. Anthropometric measurements and serum samples were collected after an 8-h fast at baseline and after the weight-reduction intervention. Subjects reduced body mass by 4%. The GWR group restricted calories over 12 d, while the RWR group restricted calories over 2 d. A series of 2 × 5 repeated-measures (RM) ANOVAs was conducted to examine differences in nutrient consumption, while separate 2 × 2 RM ANOVAs were conducted to examine differences in anthropometric measures and serum markers. When applicable, Tukey post hoc comparisons were conducted. Significance for all tests was set at P < .05. Results: There were no between-groups differences for any anthropometric measure (P > .05). Subjects in both groups experienced a significant reduction in body mass, fat mass, lean mass, and percent body fat (P < .05). There were no between-groups differences in serum markers of myostatin-pathway activity (P > .05), but subjects in the RWR condition experienced a significant increase in serum myostatin (P < .01), a decrease in follistatin (P < .01), and an increase in myostatin-to-follistatin ratio (P < .001). Conclusion: Although there were no between-groups differences for any outcome variables, the serum myostatin-to-follistatin ratio was significantly increased in the RWR group, possibly signaling the early stages of skeletal-muscle catabolism.