Two vanadium redox flow battery topologies have been compared. In the conventional series stack, bipolar plates connect cells electrically in series and hydraulically in parallel. The alternative topology consists of cells connected in parallel inside stacks by means of monopolar plates in order to reduce shunt currents along channels and manifolds. Channelled and flat current collectors interposed between cells were considered in both topologies. In order to compute the stack losses, an equivalent circuit model of a VRFB cell was built from a 2D FEM multiphysics numerical model based on Comsol®, accounting for coupled electrical, electrochemical, and charge and mass transport phenomena. Shunt currents were computed inside the cells with 3D FEM models and in the piping and manifolds by means of equivalent circuits solved with Matlab®. Hydraulic losses were computed with analytical models in piping and manifolds and with 3D numerical analyses based on ANSYS Fluent® in the cell porous electrodes. Total losses in the alternative topology resulted one order of magnitude lower than in an equivalent conventional battery. The alternative topology with channelled current collectors exhibits the lowest shunt currents and hydraulic losses, with round-trip efficiency higher by about 10%, as compared to the conventional topology.