A small proportion of postganglionic muscle sympathetic single units can be inhibited during sympathoexcitatory stressors in humans. However, whether these responses are dependent on the specific stressor or the level of sympathoexcitation remains unclear. We hypothesize that, when matched by sympathoexcitatory magnitude, different stressors can evoke similar proportions of inhibited single units. Multiunit and single-unit muscle sympathetic nerve activity (MSNA) were recorded in seven healthy young males at baseline and during 1) rhythmic handgrip exercise (40% of maximum voluntary contraction) and 2) acute isocapnic hypoxia (partial pressure of end-tidal O2 47 ± 3 mmHg). Single units were classified as activated, nonresponsive, or inhibited if the spike frequency was above, within, or below the baseline variability, respectively. By design, rhythmic handgrip and isocapnic hypoxia similarly increased multiunit total MSNA [Δ273 ± 208 vs. Δ254 ± 193 arbitrary units (AU), P = 0.84] and single-unit spike frequency (Δ8 ± 10 vs. Δ12 ± 13 spikes/min, P = 0.12). Among 19 identified single units, the proportions of activated (47% vs. 68%), nonresponsive (32% vs. 16%), and inhibited (21% vs. 16%) single units were not different between rhythmic handgrip and isocapnic hypoxia (P = 0.42). However, only 9 (47%) single units behaved with concordant response patterns across both stressors (7 activated, 1 nonresponsive, and 1 inhibited during both stressors). During the 1-min epoch with the highest increase in total MSNA during hypoxia (Δ595 ± 282 AU, P < 0.01) only one single unit was inhibited. These findings suggest that the proportions of muscle sympathetic single units inhibited during stress are associated with the level of sympathoexcitation and not the stressor per se in healthy young males.NEW & NOTEWORTHY Subpopulations of muscle sympathetic single units can be inhibited during mild sympathoexcitatory stress. We demonstrate that rhythmic handgrip exercise and isocapnic hypoxia, when matched by multiunit sympathoexcitation, induce similar proportions of single-unit inhibition, highlighting that heterogeneous single-unit response patterns are related to the level of sympathoexcitation independent of the stressor type. Interestingly, only 47% of single units behaved with concordant response patterns between stressors, suggesting the potential for functional specificity within the postganglionic neuronal pool.