Physiotherapeutic management of lumbar disorders often utilises specific segmental joint mobilisation techniques; however, there is only limited evidence of any neurophysiological effects and much of this has focused on the cervical spine and upper limbs. This study aims to extend the knowledge base underpinning the use of a unilaterally applied lumbar spinal mobilisation technique by exploring its effects on the peripheral sympathetic nervous system (SNS) of the lower limbs. Using a double blind, placebo controlled, independent groups study design and based upon power calculations, 45 normal naïve healthy males were randomly assigned to one of three experimental groups (control, placebo or treatment; a unilaterally applied postero-anterior mobilisation to the left L4/5 zygopophyseal joint). SNS activity was determined by recording skin conductance (SC) obtained from lower limb electrodes connected to a BioPac unit. Validation of the placebo technique was performed by post-intervention questionnaire. Results indicated that there was a significant change in SC from baseline levels (13.5%) that was specific to the side treated for the treatment group during the intervention period (compared to placebo and control conditions). This study provides preliminary evidence that a unilaterally applied postero-anterior mobilisation technique performed, at a rate of 2 Hz, to the left L4/5 lumbar zygopophyseal joint results in side-specific peripheral SNS changes in the lower limbs.