Microspecies involved in prototropic equilibria of isoxicam, piroxicam, meloxicam, tenoxicam, and lornoxicam are characterized by time‐dependent density functional theory (TD‐DFT) and UV‐vis spectrophotometry, their relative Gibbs free energies in solution and Maxwell–Boltzmann populations are theoretically calculated. TD‐DFT calculations of the most intense transition energies for the microspecies involved in equilibria are compared with those obtained in solvents of different dielectric constants (1,4‐dioxane, ethanol, water, and formamide) and at various pH conditions. Our TD‐DFT results allow establishing the predominant oxicam microspecies at the experimental conditions. Geometry optimizations are performed at level of theory PCM‐PBE0/6‐31+G(d, p), and transition energies are computed using the protocol PCM‐PBE0/6‐311++G(d, p). © 2012 Wiley Periodicals, Inc.