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Introduction: Sepsis is a common cause of morbidity and mortality in populations with a high prevalence of HIV, but the full package of early goal directed therapy (EGDT) for sepsis is not feasible in most low and middle-income countries. The objective was to develop emergency adult sepsis care guidelines for Botswana appropriate to available resources and local epidemiology in referral hospitals and in lower levels of care. Methods: The individual components of guidelines from the Surviving Sepsis Campaign were compared with available resources for their applicability in a tertiary referral hospital in Botswana. Antibiotics were chosen based on the hospital antibiogram, national antibiotic guidelines, and the cost and availability of antibiotics. The preliminary algorithm was presented to emergency centre medical officers in a referral hospital for feasibility and acceptability of implementation. The referral hospital guideline was further modified as part of a National Guidelines Project for suitability to all levels of care. Results: An acceptable and feasible sepsis algorithm was developed and implemented in a referral hospital in Botswana in accordance with the established hospital process. In turn, it served as the basis for the development of a national guideline. Discussion: The principles of EGDT are adaptable to Botswana, and are likely to be adaptable to a variety of low- and middle-income countries on the basis of local resources and epidemiology. Further research is needed to study adherence and outcome related to the modified guidelines.