The vast majority of surface structures are located on or surrounded by unsaturated soil deposits and may suffer excessive settlements during earthquakes. However, the fundamental understanding of the mechanisms by which the degree of saturation impacts the volumetric deformation of soils during seismic loading is still not mature. Consequently, it is critical to develop and calibrate seismic compression models while considering these mechanisms. The objective of this paper is to experimentally investigate the impacts of the degree of saturation, fines content, and desaturation technique on the seismic compression of sand and silty sands. The experimental program involved undrained cyclic direct simple shear tests on specimens prepared using suction control and wet-compaction techniques with similar relative densities but different levels of saturation. A strain-based predictive model was adapted and modified to capture the observed trends in the seismic compression of soils with different degrees of saturation. The suitability and applicability of the model were verified by comparing the measured and estimated compression values in this study with ones reported in the literature for other soils and desaturation approaches.