IntroductionThe economic and health burden of sexually transmitted and genital infections (henceforth, STIs) in low-income and middle-income countries (LMICs) is substantial. Left untreated, STIs during pregnancy may result in several adverse pregnancy and birth outcomes. Timely diagnosis and treatment at point-of-care (POC) can potentially improve these outcomes. Despite the availability and promotion of POC diagnostics for STIs as a key component of antenatal care in LMICs, their widespread use has been limited, owing to the high economic costs faced by individuals and health systems. To date, there have been no systematic reviews which explore the cost or cost-effectiveness of POC testing and treatment of STIs in pregnancy in LMICs. The objective of this protocol is to outline the methods that will compare, synthesise and appraise the existing literature in this domain.Methods and analysisWe will conduct literature searches in MEDLINE, Embase and Web of Science. To find additional literature, we will search Google Scholar and hand search reference lists of included papers. Two reviewers will independently search databases, screen titles, abstracts and full texts; when necessary a third reviewer will resolve disputes. Only cost and cost-effectiveness studies of POC testing and treatment of STIs, including syphilis, chlamydia, trichomonas, gonorrhoea and bacterial vaginosis, in pregnancy in LMICs will be included. Published checklists will be used to assess quality of reporting practices and methodological approaches. We will also assess risk of publication bias. Interstudy heterogeneity will be assessed and depending on variation between studies, a meta-analysis or narrative synthesis will be conducted.Ethics and disseminationEthical approval is not required as the review will use published literature. The results will be published in a peer-reviewed open source journal and presented at an international conference.PROSPERO registration numberCRD42018109072.