The adsorption efficiency of a high silica zeolite Y towards sulfamethoxazole, a sulfonamide antibiotic, was evaluated in the presence of two humic monomers, vanillin and caffeic acid, representative of phenolic compounds usually occurring in water bodies, owing their dimension comparable to those of the zeolite microporosity. In the entire range of investigated pH (5-8), adsorption of vanillin, as a single component, was reversible whereas it was irreversible for sulfamethoxazole. In equimolar ternary mixtures, vanillin coadsorbed with sulfamethoxazole, conversely to what observed for caffeic acid, accordingly to their adsorption kinetics and pKa values. Lower and higher adsorptions were observed for sulfamethoxazole and vanillin, respectively, than what it was observed as single components, clearly revealing guest-guest interactions. An adduct formed through H-bonding between the carbonyl oxygen of vanillin and the heterocycle NH of sulfamethoxazole in amide form was observed in the zeolite pore by combined FTIR and Rietveld analysis, in agreement with Density Functional Theory calculations of the adduct stabilization energies. The formation of similar adducts, able to stabilize other naturally occurring phenolic compounds in the microporosities of hydrophobic sorbents, was proposed.