Hydration of heterocyclic molecules plays a crucial role in biological and chemical recognition. Here, we present an infrared (IR) spectroscopic investigation of microhydrated, heterocyclic isoxazole molecule. The IR spectra of isoxazole-(water)n≤2 clusters are recorded using helium nanodroplet spectroscopy and are analyzed by quantum chemical calculations at the MP2/6-311++g(d,p) level. In the most abundant isoxazole-water dimer, the solvent water participates in a N···HO hydrogen bonding (H-bond) interaction, while in another observed structure, water simultaneously interacts with ring nitrogen and the neighboring CH group via N···HO and CH···O H-bonds. The addition of another water molecule to the monohydrated cluster results in the formation of a single isomer that features a seven-membered ring, in which the water dimer simultaneously interacts with skeletal nitrogen and the adjacent CH group through N···HO and CH···O bonds.