Controlled microsolvation of protonated aromatic biomolecules with water is fundamental to understand proton transfer reactions in aqueous environments. We measured infrared photodissociation (IRPD) spectra of mass-selected microhydrates of protonated 5-hydroxyindole (5HIH⁺–W_n, W = H₂O, n = 1–3) in the OH and NH stretch ranges (2700–3800 cm⁻¹), which are sensitive to the spectroscopic characteristics of interior solvation, water network formation, and proton transfer to solvent. Analysis of the IRPD spectra by dispersion-corrected density functional theory calculations (B3LYP-D3/aug-cc-pVTZ) reveals the coexistence of C3- and C4-protonated carbenium ions, 5HIH⁺(C3) and 5HIH⁺(C4), as well as the O-protonated oxonium ion, 5HIH⁺(O). Monohydrated 5HIH⁺–W clusters are formed by hydrogen-bonding (H-bonding) of the first water to the most acidic functional group, namely, the NH group in the case of 5HIH⁺(C3), the OH group for 5HIH⁺(C4), and the OH₂ group for 5HIH⁺(O). The latter benefits from its twofold degeneracy and the outstandingly high binding energy of D₀ ∼ 100 kJ mol⁻¹. Larger 5HIH⁺–W_2/3 clusters preferably grow (i) by H-bonding of the second water to the remaining vacant functional group and and/or (ii) by formation of W₂ water chains at the respective most acidic functional group. Our IRPD spectra of 5HIH⁺–W_n do not indicate any proton transfer to the solvent up to n = 3, in line with the proton affinities of 5HI and W_n. Comparison of 5HIH⁺–W_n to neutral 5HI–W and cationic 5HI⁺–W_n clusters elucidates the impact of different charge states on the topology of the initial solvation shell. Furthermore, to access the influence of the size of the arene ion and a second functional group, we draw a comparison to microhydration of protonated phenol.