IntroductionDepression and alcohol use disorders are international public health priorities for which there is a substantial treatment gap. Brief mental health interventions delivered by lay health workers in primary care services may reduce this gap. There is limited economic evidence assessing the cost-effectiveness of such interventions in low-income and middle-income countries. This paper describes the proposed economic evaluation of a health systems intervention testing the effectiveness, cost-effectiveness and cost-utility of two task-sharing approaches to integrating services for common mental disorders with HIV and diabetes primary care services.Methods and analysisThis evaluation will be conducted as part of a three-armed cluster randomised controlled trial of clinical effectiveness. Trial clinical outcome measures will include primary outcomes for risk of depression and alcohol use, and secondary outcomes for risk of chronic disease (HIV and diabetes) treatment failure. The cost-effectiveness analysis will evaluate cost per unit change in Alcohol Use Disorder Identification Test and Centre for Epidemiological Studies scale on Depression scores as well as cost per unit change in HIV RNA viral load and haemoglobin A1c, producing results of provider and patient cost per patient year for each study arm and chronic disease. The cost utility analyses will provide results of cost per quality-adjusted life year gained. Additional analyses relevant for implementation including budget impact analyses will be conducted to inform the development of a business case for scaling up the country’s investment in mental health services.Ethics and disseminationThe Western Cape Department of Health (WCDoH) (WC2016_RP6_9), the South African Medical Research Council (EC 004-2/2015), the University of Cape Town (089/2015) and Oxford University (OxTREC 2–17) provided ethical approval for this study. Results dissemination will include policy briefs, social media, peer-reviewed papers, a policy dialogue workshop and press briefings.Trial registration numberPACTR201610001825405.