Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex condition characterised by persistent fatigue amongst other symptoms. Potentially, altered motoneuron behaviour could contribute to the muscle weakness and increased effort in performing motor tasks that are sometimes reported⁽¹⁾. In particular, motoneuron persistent inward current (PIC) activity is essential to produce strong muscle contractions and depends on monoamine neuromodulation, which may be disrupted in ME/CFS⁽²⁾. Hence, this study compared PIC activity in individuals with and without ME/CFS. Individuals with ME/CFS (n=7, 3F, 45±11y) and healthy controls (n=6, 2F, 37±9y) performed ankle dorsiflexor submaximal voluntary ramp contractions (20-s duration) at 10% and 30% maximum voluntary force (MVF) while high-density electromyography recorded motor unit activity from tibialis anterior. After decomposition, ΔF was calculated as an indicator of PIC activity level. A 10-point OMNI scale assessed perceived effort during contractions. A mixed-effects model compared motoneuron data between groups. Individuals with ME/CFS reported greater perceived effort during submaximal contractions than healthy controls (10%MVF contractions: 5.2±2.2 vs. 1.3±0.5 [p=0.003], 30%MVF contractions: 5.7± 2.0 vs. 3.2±1.0 [p=0.017]). Overall, ΔF was ~24% lower (3.26 vs. 4.27 pulses/s, p=0.01) in people with ME/CFS. ΔF appeared higher in 30%MVF than 10%MVF contractions for healthy controls (4.83 vs. 3.79 pulse/s) but not individuals with ME/CFS (3.41 vs. 3.11 pulses/s). These preliminary results suggest that impaired motoneuron behaviour in ME/CFS is accompanied by greater perceived effort to perform muscular contractions. Less increase in ΔF at higher force levels may indicate impaired monoaminergic input to motoneurons in individuals with ME/CFS.