Purpose: Sleep deprivation (SD) is characterized by reduced cognitive capabilities and endurance exercise performance and increased perceived exertion (RPE) during exercise. The combined effects of SD and exercise-induced changes in neuromuscular function and cognition are unknown. This study aimed to determine whether central fatigue is greater with SD, and if so, whether this corresponds to diminished cognitive and physical responses. Methods: Twelve active males performed two 2-d conditions (SD and control (CO)). On day 1, subjects performed baseline cognitive and neuromuscular testing. After one night of SD or normal sleep, subjects repeated day 1 testing and then performed 40-min submaximal cycling and a cycling test to task failure. Neuromuscular and cognitive functions were evaluated during the cycling protocol and at task failure. Results: After SD, exercise time to task failure was shorter (1137 +/- 253 vs 1236 +/- 282 s, P = 0.013) and RPE during 40 min submaximal cycling was greater (P = 0.009) than that in CO. Maximal peripheral voluntary activation decreased by 7% (P = 0.003) and cortical voluntary activation tended to decrease by 5% (P = 0.059) with exercise. No other differences in neuromuscular function or cognitive control were observed between conditions. After SD, mean reaction time was 8% longer (P = 0.011) and cognitive response omission rate before cycling was higher (P < 0.05) than that in CO. Acute submaximal exercise counteracted cognitive performance deterioration in SD. Conclusions: One night of complete SD resulted in decreased time to task failure and cognitive performance and higher RPE compared with the control condition. The lack of difference in neuromuscular function between CO and SD indicates that decreased SD exercise performance was probably not caused by increased muscular or central fatigue.