Sepsis is a life-threatening condition requiring timely antimicrobial treatment. However, inappropriate antimicrobial use exacerbates antimicrobial resistance (AMR), creating a tension between treating sepsis promptly and minimising antimicrobial overuse. Despite numerous policies and significant research related to sepsis and AMR, there remains a persistent gap between recommendations and real-world practice due to system factors that impact normal work in all healthcare contexts. The aim of this scoping review is to understand how systems approaches have been used to study the use and governance of antimicrobials in clinical work. Methodsd analysis The scoping review protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Empirical research, reviews, protocols, theses/dissertations and quality improvement projects across all healthcare settings will be included if a primary focus includes studying antimicrobial use from a systems perspective. Searches will be conducted in EMBASE, MEDLINE and CINAHL with grey literature searching and backward citation tracking. Data on the geography and contexts studied, use of system theory, study design, approaches to data collection and analysis, limitations and implications will be extracted. Quantitative data will be categorised and qualitative data will be analysed thematically. Ethical approval is not required for the use of secondary, published data. Findings will be disseminated through academic publications and national and international presentations. Insights will be used to inform improvement work and empirical research to better support the sepsis-antimicrobial stewardship tension across multiple organisational levels.