The aim of the study was to evaluate the effect of plyometric training (PT) on central and peripheral (muscle) fatigue in prepubertal girls and boys. The boys ( n = 13, age 10.3 ± 0.3 years) and girls (n = 13, age, 10.2 ± 0.3 years) performedcontinuous 2-min maximal voluntary contractions (MVCs) before and after 16 high-intensity PT sessions. PT comprised two training sessions per week of 30 jumps in each session with 20 s between jumps. The greatest effect of PT was on excitation–contraction coupling, (twitch force increased by 323% in boys and 21% in girls) and height of a counter–movement jump (increased by 37% in boys and 38% in girls). In contrast, the quadriceps voluntary activation index, central activation ratio, and MVC did not change significantly after PT. The thickness of the quadriceps muscle increased by 9% in boys and 14% in girls after PT. In conclusion, boys and girls demonstrated similar changes in indicators of central fatigue (50–60% decrease) and peripheral fatigue (45–55% decrease) after MVC before and after PT.