Hydraulic manifolds are used to realize compact circuit layout, but may introduce a high pressure drop in the system. Their design is in fact oriented more toward achieving minimum size and weight than to reducing pressure losses. This work studies the pressure losses in hydraulic manifolds using different methods: Computational Fluid Dynamic (CFD) analysis; semi-empirical formulation derived from the scientific literature, when available; and experimental characterization. The purpose is to obtain the pressure losses when the channels' connections within the manifold are not ascribable to the few classic cases studied in the literature, in particular for 90° bends (elbows) with expansion/contraction and offset intersection of channels. Moreover, since CFD analysis is used to predict pressure losses, general considerations of the manifold design may be outlined and this will help the design process in the optimization of flow passages. The main results obtained show how CFD analysis overestimates the experimental results; nevertheless, the numerical analysis represents the correct trends of the pressure losses.