This study examined fatigue profile during intermittent exercise in 10 men with mild to moderate mental retardation (MR) and 10 men without mental retardation (C). They performed 4 x 30s maximal knee extensions and flexions with 1-min rest on an isokinetic dynamometer. Peak torque of flexors (PTFL) and extensors (PTEX), total work (TW), and lactate were measured. Fatigue was calculated as the magnitude of decline (%) in PTFL, PTEX, and TW and as rate of decline (linear slope) in TW from 1st to 4th set. MR had lower PTFL, PTEX, TW, and lactate throughout the protocol than C, while pre-motor time was greater in MR vs. C (p<0.05). MR demonstrated a delayed pattern of reduction in muscular performance. Lower values were observed in MR vs. C in the magnitude of decline for PTEX and TW and the rate of decline for TW. In conclusion, MR exhibit a different fatigue profile during intermittent exercise than C. The lower magnitude and decline rate in neuromuscular performance in MR during intermittent exercise is associated with their lower peak strength, short-term anaerobic capacity, and lactate accumulation. Rehabilitation and sport professionals should consider the differences in fatigue profile when designing intermittent exercise programs for MR.