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Supplemental Digital Content is Available in the Text. There is evidence that joint and nerve mobilisations compared with sham or no intervention positively influence various neuroimmune responses in animal and human neuromusculoskeletal conditions., Several animal and human studies revealed that joint and nerve mobilisations positively influence neuroimmune responses in neuromusculoskeletal conditions. However, no systematic review and meta-analysis has been performed. Therefore, this study aimed to synthesize the effects of joint and nerve mobilisation compared with sham or no intervention on neuroimmune responses in animals and humans with neuromusculoskeletal conditions. Four electronic databases were searched for controlled trials. Two reviewers independently selected studies, extracted data, assessed the risk of bias, and graded the certainty of the evidence. Where possible, meta-analyses using random effects models were used to pool the results. Preliminary evidence from 13 animal studies report neuroimmune responses after joint and nerve mobilisations. In neuropathic pain models, meta-analysis revealed decreased spinal cord levels of glial fibrillary acidic protein, dorsal root ganglion levels of interleukin-1β, number of dorsal root ganglion nonneuronal cells, and increased spinal cord interleukin-10 levels. The 5 included human studies showed mixed effects of spinal manipulation on salivary/serum cortisol levels in people with spinal pain, and no significant effects on serum β-endorphin or interleukin-1β levels in people with spinal pain. There is evidence that joint and nerve mobilisations positively influence various neuroimmune responses. However, as most findings are based on single studies, the certainty of the evidence is low to very low. Further studies are needed.