Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. A search for the underlying cause of infection typically includes radiological imaging as part of this investigation. This document focuses on thoracic and abdominopelvic causes of sepsis. In 2017, the global incidence of sepsis was estimated to be 48.9 million cases, with 11 million sepsis-related deaths (accounting for nearly 20% of all global deaths); therefore, understanding which imaging modalities and types of studies are acceptable or not acceptable is imperative. The 5 variants provided include the most commonly encountered scenarios in the setting of sepsis along with recommendations and data for each imaging study. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.