The Generation IV International Forum (GIF) Proliferation Resistance and Physical Protection (PR&PP) Working Group has developed a methodology for the PR&PP evaluation of advanced nuclear energy systems (NESs). A notional sodium-cooled fast neutron nuclear reactor system, named the Example Sodium Fast Reactor (ESFR), was used as a case study for the development and demonstration of the GIF PR&PP evaluation methodology. This paper presents some of the results of the application of the GIF PR&PP evaluation methodology to a misuse scenario involving the ESFR. The ESFR baseline design and two design variations are addressed. Rather than presenting a complete evaluation of all the possible misuse scenarios, the paper concentrates on methodological aspects and illustrates how a qualitative analysis following the GIF PR&PP evaluation methodology can generate traceable results of the considered design variations and provide useful feedback for both system and safeguards designers as well.