The optimal intra-set rest in cluster sets (CLS) plyometric-jump training (PJT) to improve physical fitness remains unclear. Thus, this study compared the effects of PJT with traditional (TRS) vs. CLS structures using different intra-set rests on physical fitness components. Forty-seven recreationally active young men performed 3-5 sets of 10-12 repetitions of upper- and lower-body exercises twice a week for six weeks using different set configurations as the TRS group (no intra-set rest), and the CLS10, CLS20 and CLS30 groups with 10, 20 and 30 s intra-set rest, respectively, while the total rest period (i.e., 180 s) was equated. Testing was carried out 48 h before and after the intervention and the rating of fatigue (ROF) was also assessed 20 min after the first and last session. There was no significant difference in the mean energy intake between groups (p > 0.05). The ANCOVA revealed that all groups showed similar improvements (p < 0.05) in body mass, body mass index, fat-free mass, one repetition maximum (dynamic strength) and repetitions to failure (muscular endurance) in back squat and chest press, handgrip strength, standing long jump, 20 m sprint, and 9-m shuttle run (change of direction speed), whereas the ROF decreases were greater in the CLS20 and CLS30 groups (p < 0.05). Compared to the TRS structure, six weeks of PJT with an intra-set rest of 20 s, or 30 s induced similar improvements in the measures of physical fitness and anthropometrics, with lower exercise-induced fatigue perception.