Links between the mechanisms and kinetics of aqueous and dry thermal oxidation of porous silicon (pSi) microparticles have been investigated and the influence on molecular interaction established. zeta potential measurements have established the interplay between the dry oxidation state of pSi microparticles and their interfacial chemistry in aqueous solution, and Fourier transform infrared spectroscopy has demonstrated the effect of immersion time and oxidation temperature on surface chemistry. The influence of aqueous and thermal oxidation on molecular interactions and loading was investigated using methylene blue as a probe molecule. Aqueous immersion of pSi microparticles results in an initial increase in OySiH (y = 1-3) species with increasing immersion times, reducing O2SiH concentration, while O3SiH concentration remained constant. Thermal oxidation from 473 to 1073 K causes the gradual transition from SiySiHx to OySiH and finally OySiOH species. Both aqueous and thermal oxidations had an effect on the zeta potentials of pSi microparticles. Methylene blue discoloration occurred due to its reduction by the SiSiHx-terminated surface thereby demonstrating the reactivity of such species. Aqueous and thermal oxidations modify pSi microparticle surface chemistry, which has therefore shown to influence molecular interactions. Understanding the aqueous oxidation of pSi is crucial when loading pSi from aqueous solution due to its impact on molecular interactions. These molecular interactions play an important role in the loading of pSi since they dictate the attraction of the molecule toward the surface and therefore ultimately the loading level.