BackgroundChronic pain is a common public health problem with negative consequences for individuals and societies. Fortunately, interdisciplinary chronic pain management has been shown to be effective for improving patients’ outcomes and strongly recommended in clinical practice guidelines. Appropriate referral within the healthcare system based on individuals’ needs and available services is essential to optimise health-related outcomes and maximise resources. Clinical decision support systems have been shown to be effective for supporting healthcare professionals in different practices. However, there is no knowledge synthesis on clinical decision support systems for referral within chronic pain practice. We aim to identify the clinical decision support systems for referral within chronic pain practices and assess their content, effectiveness, harms, and validation parameters.MethodsUsing the methodology of Cochrane reviews, we will perform a systematic review and meta-analysis based on studies meeting the following criteria: Population, patients with chronic pain and/or healthcare professionals working in chronic pain; Intervention, clinical decision support systems for referral within chronic pain practice; Comparison, any other clinical tool, any usual care or practices; Outcomes, clinical outcomes of patients measuring how patients feel, function or survive including benefits, adverse effects, continuity of care, care appropriateness, care satisfaction, quality of life, healthcare professional performance, and cost outcomes; and Study design: randomized controlled trials, non-randomized controlled trials, before and after controlled studies and interrupted time series. We will search relevant literature with the support of an information specialist using Medline, Embase, PsycInfo, CINHAL, Web of Science and Cochrane Library from their inception onwards. Two reviewers will independently complete study selection, data extraction and risk of bias assessment. We will analyse data to perform both narrative syntheses and meta-analysis if appropriate.DiscussionFindings of this review will contribute to enhancing chronic pain care and research. Clinical decision support systems identified as effective in this review can be investigated for implementation in clinical practice and impact on improving patient, clinical and health system outcomes. Clinical decision support systems not yet ready for implementation that require further improvement will also be identified.Systematic review registrationPROSPERO registration: CRD42020158880.