Leptospirosis is a significant public health concern worldwide, as it imposes a substantial economic burden on the global economy. Despite a comprehensive search of the relevant literature, few studies evaluating the economic burden experienced by leptospirosis patients were identified. In particular, very few studies thoroughly examined the cost components, including direct, indirect and intangible costs. This paucity of evidence further motivates the need to conduct a more focused search using a systematic review approach. Thus, this study aims to systematically review the global literature on the magnitude and aspects of the direct, indirect and intangible costs incurred by leptospirosis patients and the methods available for assessing these costs.

This review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols 2015 guidelines. The Population, Intervention, Comparison, Outcomes, Study Design framework was used to develop the review questions. The search strategy will comprise two key term blocks: ‘Leptospirosis’ and ‘Economic cost’. A comprehensive literature search will be conducted in PubMed, Web of Science, Scopus, MEDLINE, CINAHL, the Cochrane Library, EconStor and IDEAS to collect publications from inception to July 2025. The search will be limited only to English-language and peer-reviewed publications. The Mixed Methods Appraisal Tool will be used to assess the quality of eligible studies. Extracted cost data will be categorised into direct, indirect and intangible costs. A meta-analysis will be conducted to quantify the magnitude of these costs if sufficient methodological and contextual homogeneity exists. Moreover, a narrative synthesis will be performed to analyse the qualitative data related to intangible costs.

As this study will use secondary data, ethical approval is not required. The systematic review’s findings will be published in a scientific journal and presented at relevant conferences to address the knowledge gap regarding the economic burden (including direct, indirect and intangible costs) faced by leptospirosis patients. The results of this systematic review will guide policies for prioritising prevention, improving surveillance and efficiently allocating resources to control leptospirosis.

PROSPERO CRD 42024585056.