Background A significant cause of morbidity and mortality during pregnancy is maternal anaemia. The causes of anaemia and the sequelae are varied, and the prevention and management are public health challenges, especially in resource limited settings and certain geographic locations. South Africa is plagued by a quadruple burden of disease, with high maternal mortality rates affected by hypertensive disorders of pregnancy, HIV, tuberculosis and neglected tropical diseases. This is most prevalent in people of lower socio-economic status. Poor nutrition, chronic infections, lack of access to health care facilities and poor compliance with micronutrient supplementation all contribute to maternal anaemia. The aim of this study is to systematically map the literature to ascertain the pooled prevalence and associated causes of anaemia in the South African pregnant population, which will enable health care workers and other key stakeholders to more pertinently address Sustainable Development Goal 3 focussing on good health and reducing maternal mortality.Methods PubMed, CINAHL, EMBASE, EBSCO, Ovid maternity and infant care databases, Cochrane Database of Systematic Reviews, Web of Science and SCOPUS will be searched, using the keywords ‘anaemia’, ,’haemoglobin’, ‘pregnancy’, ‘South Africa’, to conduct a systematic review and meta-analysis to explore, describe and map literature on the distribution and burden of anaemia in pregnant women in South Africa. The reference list of articles selected for review will be scanned for other articles of interest to our study question. Studies published in any language will be included in this review. As there may be differences in sampled populations in South Africa based on geography and sociodemographic factors, a weighted inverse-variance meta-analysis using a random-effects model will be carried out to generate a pooled prevalence estimate. A Funnel plot and Egger’s regression test will be conducted to assess publication bias. Heterogeneity among studies will be checked using I2 to determine dispersion and meta-regression analysis will be performed to investigate the source of heterogeneity. The articles obtained by these searches will be analysed for causative factors, severity and outcomes by a parallel and independent review team, using suitable eligibility criteria. Screening, data extraction, and quality appraisal will be conducted independently by two authors. Disagreement will be resolved by independent assessment by a third reviewer. Sub group analysis by region, stage of pregnancy, socio-economic status, severity and cause of anaemia will be conducted if sufficient data is available. Data will be analysed using statistical software, and presented in evidence tables and in meta-analytic forest plots.Discussion This protocol is developed to systematically review the literature on the prevalence and severity of anaemia, risk factors and outcomes in pregnant women in South Africa. Correlation of factors contributing to the development of anaemia and other disorders during pregnancy will facilitate exploration of appropriate medical and behavioural change interventions implemented within other countries or regions that mitigate risk. This study will assist local health systems to inform public health policies and practises for more favourable maternal and fetal outcomes.