Motoneuronal persistent inward currents (PICs) are both facilitated by neuromodulatory inputs and highly sensitive to local inhibitory circuits (e.g., Ia reciprocal inhibition). Methods aimed to increase group Ia reciprocal inhibition from the antagonistic muscle have been successful in decreasing PICs, and the diffuse actions of neuromodulators released during activation of remote muscles have increased PICs. However, it remains unknown how motoneurons function in the presence of simultaneous excitatory and inhibitory commands. To probe this topic, we investigated motor unit (MU) discharge patterns and estimated PICs during voluntary co-contraction of ankle muscles, which simultaneously demands the contraction of agonist-antagonist pairs. Twenty young adults randomly performed triangular ramps (10s up and down) of both co-contraction (simultaneous dorsiflexion and plantarflexion) and isometric dorsiflexion to a peak of 30% of their maximum muscle activity from a maximal voluntary contraction. Motor unit spike trains were decomposed from high-density surface electromyography recorded over the tibialis anterior (TA) using blind source separation algorithms. Voluntary co-contraction altered motor unit discharge rate characteristics, decreasing estimates of PICs by 20% (4.47 pulses per second (pps) vs 5.57 pps during isometric dorsiflexion). These findings suggest that, during voluntary co-contraction, the inhibitory input from the antagonist muscle overcomes the additional excitatory and neuromodulatory drive that may occur due to the co-contraction of the antagonist muscle, which constrains PIC behavior.