The DFT calculations presented in this work show that 5-FU adsorbed in all-silica FAU is primarily stabilised through dispersion interactions, with hydrogen bonds to framework oxygen atoms playing only a minor role. In protonic zeolites, a significant stabilisation arises from interactions of carbonyl O atoms with the framework protons. While framework deprotonation and concurrent formation of a positively charged 5-FU species was observed upon interaction with a single framework proton, the availability of two framework protons in proximity resulted in the formation of adsorption complexes stabilised by several hydrogen bonds, with neutral 5-FU simultaneously acting as acceptor and donor. AIMD simulations confirmed the stability of these hydrogen bonds at room temperature (in the absence of water). From a broader perspective, these results show that "multi-site" interactions, simultaneous interactions with more than one framework proton, can make a considerable contribution to the stabilisation of functional organic molecules in the pores of protonic zeolites. Such scenarios should thus be taken into account in computational studies and in the analysis of experimental data, primarily for species possessing two or more negatively polarised areas that could interact with the framework protons (or, analogously, with cations in cation-exchanged zeolites, as discussed recently for the example of the organic UV filter octyl methoxycinnamate in zeolite NaX ).