Abstract Challenges with safeguarding molten salt reactor (MSR) designs have prompted the search for enhanced safeguards technologies and revised safeguards materials control & accountancy (MC&A) approaches. A molten salt sampling system is a subsystem being developed to help support facility MC&A in future MSRs by removing salt samples from the primary fuel and/or coolant salt loop of an MSR for chemical and isotopic analysis. To consider the safeguards implications of this molten salt sampling system early in the design process, we employed a safeguards by design approach during the development of a prototype molten salt sampling system. Specifically, we identified and tailored a checklist approach to systematically evaluate the design against recognized safeguards and security attributes. This technical brief describes the molten salt sampling system design and operational concept upon which we applied the safeguards by design methodology, conveys the methods we used to employ the safeguards by design approach on the molten salt sampling system design, and discusses the preliminary results and design insights gained from this safeguards by design assessment.