Study of the energetics of confinement of small organic molecules in microporous frameworks provides essential information for rational design and application of functional porous materials. Using immersion calorimetry and temperature-programmed desorption coupled with mass spectroscopy, we describe the complex guest−host interactions of a nonpolar organic molecule (n-hexane) with a series of calcium-exchanged zeolite A materials whose pore accessibility was modified by varying the calcium content to achieve inaccessible, partially accessible, and fully accessible central cavities for n-hexane molecules. The overall magnitude and trend with the pore size of n-hexane−zeolite A interactions have been determined. In addition, the contributions to energetics from the external surface (ΔH wet), tetrahedral framework (ΔH g‑h), and adjacent n-hexane molecules (ΔH g‑g) were separated, quantified, and interpreted.