AbstractWith the advent of increasing computational power and large‐scale data acquisition, network analysis has become an attractive tool to study the organisation of complex systems and the interrelation of their constituent entities in various scientific domains. In many cases, relations only occur between entities of two different subsets, thereby forming a bipartite network. Often, the analysis of such bipartite networks involves the consideration of its two monopartite projections in order to focus on each entity subset individually as a means to deduce properties of the underlying original network. Although it is broadly acknowledged that this type of projection is not lossless, the inherent limitations of their interpretability are rarely discussed. In this work, we introduce two approaches for measuring the information loss associated with bipartite network projection. Application to two structurally distinct cases in network pharmacology, namely, drug‐target and disease‐gene bipartite networks, confirms that the major determinant of information loss is the degree of vertices omitted during the monopartite projection.