The purpose of this study was to investigate the influence of the crystallinity, surface area, and pore volume of cellulose powders on the loading, release, and stability of nicotine. Four different types of cellulose powders with varying crystallinity index, surface area, and pore volume were produced and characterized. The powders were loaded with nicotine by rotary evaporation from an ethanol solution and by adsorption from nicotine-saturated air. The release of nicotine from loaded cellulose powders into both a passing airstream and water was investigated by UV spectroscopy. A 3-month stability study was conducted and the total sum of nicotine oxidation products was measured. Nicotine loading and release were independent of cellulose powder crystallinity, whereas it was possible to load more nicotine on the cellulose powder with a large surface area and pore volume. Release into water was very rapid and almost complete for all samples. Nicotine was most stable when loaded on the powder with a large surface area and pore volume. Highly porous cellulose matrices could be useful for stabilization and handling of both nicotine and other liquid active pharmaceutical ingredients.