In this work, we examined the ground and low-lying excited states of the serotonin (SERO) molecule and of four of its water hydrogen-bonded complexes (SERO-(H2O)n, with n = 1 and 2). Density functional theory (DFT) and its time-dependent variant (TD-DFT) were used for determining, respectively, ground state properties (such as equilibrium structures and relative energetics, when applicable) and excited state parameters (vertical excitation energies, generalized oscillator strengths (GOS), and structures). The CAM-B3LYP exchange–correlation functional with the def2-TZVP basis set was used and all the computations were performed in the gas-phase and in water (through the use of the integral equation formalism polarizable continuum model, IEF-PCM). In terms of ground-state, the existence of the H⋯O–H⋯N interaction in one of the SERO-H2O conformations contributed to the stabilization of the system when compared to its corresponding counterpart, with solvation decreasing (from 3.43 kcal/mol in the gas-phase to 1.75 kcal/mol in water) the differences regarding their relative energies. While no major differences regarding the excitation energies associated to an accessible state are suggested from the comparison between the results obtained for a given system through the consideration of solvation and those corresponding determined in the gas-phase, the hydrogen-bond interactions (originating from the explicit water molecules) combined with the implicit (water) solvation may be responsible for providing synergic effects in terms of increasing both the GOS related to a given open state as well as the number of excited states accessible, suggesting an enhancement in the photoabsorption. Taking one of the SERO-(H2O)2 conformations as instance, all the five lowest-lying excited singlets of the system were determined as being accessible (having GOS from 0.1036 to 0.5664) in water while only a single excited state (with GOS = 0.1150) is expected to be open in the gas-phase environment.