Fabrication of functionalized surfaces using polymer brushes is a relatively simple process and parallels the presence of glycocalyx filaments coating the luminal surface of our vasculature. In this paper, we perform atomistic-like simulations based on dissipative particle dynamics (DPD) to study both polymer brushes and glycocalyx filaments subject to shear flow, and we apply mean-field theory to extract useful scaling arguments on their response. For polymer brushes, a weak shear flow has no effect on the brush density profile or its height, while the slip length is independent of the shear rate and is of the order of the brush mesh size as a result of screening by hydrodynamic interactions. However, for strong shear flow, the polymer brush is penetrated deeper and is deformed, with a corresponding decrease of the brush height and an increase of the slip length. The transition from the weak to the strong shear regime can be described by a simple ‘blob’ argument, leading to the scaling , where is the critical transition shear rate and is the grafting density. Furthermore, in the strong shear regime, we observe a cyclic dynamic motion of individual polymers, causing a reversal in the direction of surface flow. To study the glycocalyx layer, we first assume a homogeneous flow that ignores the discrete effects of blood cells, and we simulate microchannel flows at different flow rates. Surprisingly, we find that, at low Reynolds number, the slip length decreases with the mean flow velocity, unlike the behaviour of polymer brushes, for which the slip length remains constant under similar conditions. (The slip length and brush height are measured with respect to polymer mesh size and polymer contour length, respectively.) We also performed additional DPD simulations of blood flow in a tube with walls having a glycocalyx layer and with the deformable red blood cells modelled accurately at the spectrin level. In this case, a plasma cell-free layer is formed, with thickness more than three times the glycocalyx layer. We then find our scaling arguments based on the homogeneous flow assumption to be valid for this physiologically correct case as well. Taken together, our findings point to the opposing roles of conformational entropy and bending rigidity – dominant effects for the brush and glycocalyx, respectively – which, in turn, lead to different flow characteristics, despite the apparent similarity of the two systems.