The low-occupancy adsorption thermodynamics of n-alkanes ranging in length from C-4 to C-25 in the zeolite silicalite is predicted from molecular simulations. A bias Monte Carlo (MC) technique is described which permits these calculations to be carried out with modest computational expense. In addition, a general, systematic coarse-graining methodology is developed which enables the location and shape of chains of arbitrary length to be accurately described using a small number of degrees of freedom. By coupling this methodology with the bias Monte Carlo technique, the free energy of sorbed chains is calculated as a function of the coarse-grained configuration of chains. The results indicate that, at high temperature, n-alkanes probe all the accessible regions of the zeolite pore network, favoring high-entropy conformations that access more than one type of channel environment. As temperature decreases to room temperature, short chains continue to populate all regions of the zeolite, while chains longer than n-octane align along the straight channels in highly localized low-energy configurations. Free energy profiles of this type are also used to gain insight into probable diffusion mechanisms for the long n-alkanes at low occupancy. Macroscopic thermodynamic results, such as Henry’s law constants and isosteric heats of adsorption, are calculated and compared to experimentally obtained values. The agreement between simulation and experiment is generally good. The results presented here show that there is a strong thermodynamic driving force for adsorption at all temperatures and chain lengths studied.