ABSTRACT: Pain neuroscience education (PNE) has shown promising results in the management of patients with chronic spinal pain (CSP). However, no previous review has determined the optimal dose of PNE added to an exercise programme to achieve clinically relevant improvements. The aim was to determine the dose-response association between PNE added to an exercise programme and improvements in pain intensity and disability in patients with CSP. A systematic search of PubMed/MEDLINE, Embase, Web of Science, Scopus, and the Cochrane Library was conducted from inception to April 19, 2023. The exposure variable (dosage) was the total minutes of PNE. Outcome measures included pain intensity, disability, quality of life, pressure pain thresholds, and central sensitization inventory. Data extraction, risk-of-bias assessment, and certainty of evidence were performed by 2 independent reviewers. The dose-response relationship was assessed using a restricted cubic spline model. Twenty-six randomised controlled trials with 1852 patients were included. Meta-analysis revealed a statistically significant effect in favour of PNE on pain intensity and disability. In addition, a dose of 200 and 150 minutes of PNE added to an exercise programme was estimated to exceed the minimum clinically important difference described in the literature for pain intensity (-2.61 points, 95% CI = -3.12 to -2.10) and disability (-6.84 points, 95% CI = -7.98 to -5.70), respectively. The pooled effect of the isolated exercise was small. These findings may be useful in optimising the most appropriate PNE dose to achieve clinically relevant improvements in patients with CSP.