During fatiguing submaximal contractions a constant force production can be obtained at the cost of an increasing central command intensity. Little is known about the interaction between the underlying central mechanisms driving motor behaviour and cognitive functions. To address this issue, subjects performed four tasks: an auditory choice reaction task (CRT), a CRT simultaneously with a fatiguing or a non-fatiguing submaximal muscle contraction task, and a fatiguing submaximal contraction task alone. Results showed that performance in the single-CRT condition was relatively stable. However, in the fatiguing dual-task condition, performance levels in the cognitive CRT deteriorated drastically with time-on-task. Moreover, in the fatiguing dual-task condition the rise in force variability was significantly larger than during the fatiguing submaximal contraction alone. Thus, our results indicate a mutual interaction between cognitive functions and the central mechanisms driving motor behaviour during fatigue. The precise nature of this interference, and at what level this interaction takes place is still unknown.