OBJECTIVES: Failed back surgery syndrome (FBSS) is associated with impaired autonomic tone, characterized by sympathetic prevalence and vagal withdrawal. Although spinal cord stimulation (SCS) alleviates pain in FBSS, there is limited research investigating how SCS affects measures of autonomic function. This was a prospective, open-label, feasibility study exploring measures of autonomic function in patients with FBSS receiving SCS therapy. MATERIALS AND METHODS: A total of 14 patients with FBSS were recruited for baseline measurements and underwent a trial of 10-kHz SCS. There were three failed trials, resulting in the remaining 11 participants receiving a fully implanted 10-kHz SCS system. One participant requested an explant, resulting in ten participants completing both baseline and follow-up (three to six months after SCS implant) measurements. Autonomic function was assessed using time- and frequency-domain heart rate variability (HRV), baroreceptor reflex sensitivity (BRS), and muscle sympathetic nerve activity (MSNA) using microneurography. Because this was a feasibility study, most of the analysis was descriptive. However, paired t-tests and Wilcoxon signed-rank tests tested for differences between baseline and follow-up. RESULTS: In the whole (N = 14) and final (N = 10) samples, there was between-participant variation in baseline and follow-up measures. This, combined with a small sample, likely contributed to finding no statistically significant differences in any of the measures between baseline and follow-up. However, plotting baseline and follow-up scores for individual participants revealed that those who showed increases in MSNA frequency, square root of the mean of the squared differences between adjacent RR intervals (RMSSD), percentage of the number of RR intervals >50 ms (pRR50), total power, and up BRS between baseline and follow-up had distinct clustering of baseline values compared with those who showed decreases in these measures. CONCLUSIONS: Findings from this feasibility study will aid with informing hypotheses for future research. A key aspect that should be considered in future research concerns exploring the role of baseline measures of autonomic function in influencing change in autonomic function with SCS therapy.