The solubility of oxygen in water at different temperatures has been analysed in the light of a statistical thermodynamic model. According to the model, the oxygen–water system is considered as a convoluted ensemble consisting of a reacting system, formed by oxygen molecules and structured solvent with enthalpy difference DHf between discrete enthalpy levels, and of a non-reacting system with continuous distribution of enthalpy levels. The enthalpy change of the reaction between oxygen and water, as determined either by measuring the solubility of substances in water at different temperatures either by measuring heat calorimetrically, is partially absorbed by some nw water molecules. The relaxed water molecules occupy part of the cavity formed around solute. The part of heat absorbed, DHw depends linearly upon the temperature and causes the observed changes with temperature of apparent enthalpy DHapp for the dissolution of oxygen and many other inert substances in water. The number nw is proportional to the size of solute as shown by comparison with noble gases and other inert substances slightly soluble in water. The solubilization process of all these substances is clearly analogous.