Biopolymers, such as cellulose, can be utilized in different areas, such as replacing conventional plastics, modifications are needed to fit desirable material properties. The ability to predict how a modification to a structure can affect the materials properties by only studying their chemical structure is thus essential in order to effectively find suitable modifications. In this study, the Hansen solubility parameters (HSP), calculated from the chemical structure, are investigated for the ability to predict glass transition temperature and water interaction of cellulose esters. Namely, cellulose acetate, cellulose acetate propionate and cellulose acetate butyrate. The esters all have a similar total degree of substitution, meaning that the number of hydroxyl groups are similar, while the main difference is the side-chain length of the acyl group. The Hansen solubility parameters showed for the selected materials to primarily consist of dispersive energy, followed by hydrogen bonding energy and polar energy. It was shown that the glass transition temperature (Tg) decreased with an increased side-chain length of the acyl chain. This indicate that the strong short-range hydrogen bonds between polymer chains decreases by being pushed apart by the increasing molecular volume of the side chain, or in other words screened. This were also supported by water interaction studies, where an increase in side-chain length resulted in lower water solubility and diffusion. The individual HSP were also scrutinized, and it was concluded that for the materials studied, the polar parameter showed strongest correlation to how they interact with water.