The physical properties of drug substances may affect stability, manufacturing, dissolution and bioavailability. Variations in the degree of crystallinity in a pharmaceutical substance may exhibit physicochemical differences that impact at therapeutic, manufacturing, commercial and legal levels, yet no reference has been found on the physical properties of micronised omeprazole. This study reports on the physical and thermal characterisation of the sodium salts of S- and R-omeprazole, using diffuse reflectance infrared Fourier transform spectroscopy (DRIFT), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), microthermal analysis (microTA) and powder X-ray diffraction (XRPD). DSC experiments were performed in order to determine not only their thermal stability, but also the thermal history of both forms. SEM results indicate similar morphology, particle size and shape of powdered drug, while, microTA of processed discs shows different topographical images for S- and R-omeprazole, exhibiting a smoother surface for the S-form, indicative of the smoother particle size not evident in the SEM results. The low level of crystallinity of both enantiomers was confirmed by DRIFT spectroscopy and XRPD. Thermal stability by DSC of S- and R-omeprazole sodium salts was superior to that of the neutral omeprazole. This study has examined the physical and thermal properties of both forms and in highlighting their differences provides an explanation for the potential differences in bioavailability and therapeutic efficacy.