Non-local muscle fatigue (NLMF) has been attributed to both physical and mental fatigue. The purpose of this study was to investigate the effects of mental exertion versus unilateral physical fatigue on NLMF. Sixteen recreationally active participants completed a physical task (2-sets of 100-s unilateral knee extension (KE) maximal voluntary isometric contractions (MVIC) with the dominant leg with 40-s recovery between sets, mental task (4-minute Stroop task), and control condition. Before and after each condition, blood lactate was collected, and contralateral 5-s KE, flexion (KF) and bilateral lateral trunk flexors MVIC (measure of trunk stability strength) was performed. Following the post-test 5-s MVICs, participants performed 12 non-dominant KE MVICs with a work-to-rest ratio of 5/10-s. Electromyography was monitored during the MVICs. Neither the 4-minute Stroop test or the unilateral KE physical fatigue intervention adversely affected the non-dominant KE forces or EMG activity with a single MVIC or 12 repetition MVICs. Although the non-dominant KF fatigue index forces and hamstrings EMG were not impaired by the interventions, there was a significant interaction (p = 0.001) small magnitude (d = 0.42) decrease in the non-dominant KF single MVIC force following the contralateral fatigue intervention, albeit with no significant change in hamstrings EMG. This MVIC deficit may be related to the significant decrease in dominant (p = 0.046, d = 2.6) and non-dominant external obliques (p = 0.048, d = 0.57) activation adversely affecting trunk stability. In conclusion, a 4-minute Stroop test or unilateral KE physical fatigue intervention did not impair non-dominant KE single or repeated 12 repetition MVIC forces or EMG activity. The small magnitude deficit in the non-dominant KF single MVIC force following the contralateral fatigue intervention are in accord with the heterogenous findings common in the literature.

• Non-local muscle fatigue (NLMF) was not evident when testing the force output or EMG activity of knee extension single or repeated (12) maximal voluntary isometric contractions following a mental task (Stroop test) or unilateral knee extensors physical fatigue.

• A small magnitude decrease in the non-dominant knee flexors single discrete MVIC force following the contralateral fatigue intervention was observed, but with no significant change in hamstrings EMG activity.

• The knee flexors NLMF might be attributed to decreased EMG activity of the external oblique muscles which contribute to core stability.