The activity of the sympathetic nervous system is significant to manual therapists, since the experience of pain is related to sympathetic activity. There has not been much investigation into the effects of mobilizing vertebral segments below the cervical spine. In addition to this, a synthesis of the evidence for changes in sympathetic outcome measures has not been completed. The primary objective of this review was to investigate the effects of spinal mobilizations compared to a control or placebo on sympathetic outcome measures. The secondary aim was to establish the level of change, either excitatory or inhibitory, in sympathetic outcome measures. Five electronic databases (Ovid Medline, Embase, AMED, PEDro, and the Cochrane library; from database inception to May 2012) were searched for randomized controlled trials. Two independent raters applied inclusion criteria and rated studies for methodological quality. Seven studies met the inclusion criteria. All studies exhibited a consistent increase in sympathetic outcome measures, indicative of sympathetic excitation, irrespective of the segments mobilized. Synthesis of the results established strong evidence (multiple high-quality randomised controlled trials (RCTs) for a positive change in skin conductance, respiratory rate, blood pressure, and heart rate among the healthy population. As only one study investigated changes in a symptomatic population, there was limited evidence (one RCT) for an increase in skin conductance and decrease in skin temperature. Evidence from this systematic review supports a sympatho-excitatory response to spinal mobilizations regardless of the segment mobilized.