Lowland-dwelling populations exhibit persistent sympathetic hyperactivity at altitude that alters vascular function. High-altitude populations, such as Sherpa, have previously exhibited greater peripheral blood flow in response to acute stress than Lowlanders, which may be explained through lower sympathetic activity. Our purpose was to determine whether Sherpa exhibit lower sympathetic reactivity to stress than Lowlanders. Muscle sympathetic nerve activity (MSNA; microneurography) was measured at rest in Lowlanders ( n = 14; age = 27 ± 6 yr) at 344 m and between 1 and 10 days at 5,050 m. Sherpa (age = 32 ± 11 yr) were tested at 5,050 m ( n = 8). Neurovascular reactivity (i.e., change in MSNA patterns) was measured during maximal end-expiratory apnea, isometric hand grip (IHG; 30% maximal voluntary contraction for 2-min), and postexercise circulatory occlusion (PECO; 3 min). Burst frequency (bursts/min) and incidence (bursts/100 heartbeats) and total normalized SNA (arbitrary units/min) were analyzed at rest, immediately before apnea breakpoint, and during the last minute of IHG and PECO. Vascular responses to apnea, IHG, and PECO were also measured. MSNA reactivity to apnea was smaller in Sherpa than Lowlanders at 5,050 m, although blood pressure responses were similar between groups. MSNA increases in Lowlanders during apnea at 5,050 m were significantly lower than at 344 m ( P < 0.05), indicating that a possible sympathetic ceiling was reached in Lowlanders at 5,050 m. MSNA increased similarly during IHG and PECO in Lowlanders at both 334 m and 5,050 m and in Sherpa at 5,050 m, while vascular changes (mean brachial arterial pressure, contralateral brachial flow and resistance) were similar between groups. Sherpa demonstrate overall lower sympathetic reactivity that may be a result of heightened vascular responsiveness to potential apneic stress at altitude.