The paper structure heavily influences the initial part of the out-of-plane compression curve of paperboard, and due to this, the initial part is often overlooked or disregarded. In the context of contact printing, however, surface roughness is vital to attain print uniformity. The present study delves into the effect of surface roughness of commercial paperboard and how it affects the compression response. A finite element (FE) model of a compression test has been constructed. The approach exercised in this study systematically varies the roughness and morphology of a simulated paperboard in the FE-model. The simulations are carried out with commercial software and material models, and the focus is on the structural variations in the sheet. The initial curvature of the compression curve is quantified using the initial energy. The simulations also enable the study of the stress variations underneath the compression probe. The study shows that both the surface roughness’ magnitude and spatial characteristics, as well as the relative placement of the roughness on top- and back side, will affect the initial energy. Additionally, the stress variations show that cases with similar initial energy can have their cause in different mechanisms. Therefore, the local contact conditions and pressure uniformity might not be visible in the global compression response