Ischaemic preconditioning (IPC) is a procedure in which tissue is exposed to brief, alternating periods of ischaemia and reperfusion. IPC has been shown to delay the development of fatigue, which is suggested to be caused by changes in central motor output; however, this remains speculative. We hypothesised that IPC would delay the development of fatigue by changing the central motor output, resulting in a smaller inhibition of corticospinal excitability, voluntary activation and contractile properties. Ten healthy males completed a fatiguing protocol consisting of 90 isokinetic contractions of the dorsiflexor muscles following treatment of either IPC (4x5 min 250 mmHg) or sham (4x5 min 20 mmHg) on two occasions separated by a minimum of seven days. Supramaximal stimulation of the common peroneal nerve was utilized to examine voluntary activation (VA) and potentiated twitch torque (PT) during maximal voluntary contractions at baseline, preceding the fatigue protocol (pre) and after the fatigue protocol (post). Transcranial magnetic stimulation was utilized to examine corticospinal excitability at baseline, pre and post. Tissue oxygenation using near-infrared spectroscopy and surface electromyographic activity was measured during the intervention. Across conditions, the maximal torque was significantly decreased by 49.8% from baseline and 48.2% from pre compared to post (p < 0.001) but no difference was found between the conditions (p = 0.981). VA and PT showed no significant differences. Corticospinal excitability was decreased at post measurements compared to baseline (all intensities, p’s ≤ 0.048) and pre (intensities 110-140% resting motor threshold, p’s ≤ 0.02). The fatigue protocol was divided into 10 intervals as a mean power output of three contractions at each interval throughout the protocol. Power output during the fatigue protocol decreased from interval 1 to interval 6-10 (p’s ≤ 0.04), from interval 2 to interval 3-10 (p’s ≤ 0.026) and from interval 3 to interval 4 and 6-10 (p’s ≤ 0.048). The oxygenation during the fatigue protocol showed no differences for oxygenated or deoxygenated haemoglobin between conditions or interval, but total haemoglobin was higher for IPC than sham (p = 0.003) and total haemoglobin rose during the fatigue protocol. These findings indicate that IPC did not delay the development of fatigue nor alter central motor output. Thus, IPC may not have important implications for central motor output during fatiguing exercise.