This study considers CFD simulations with conjugate heat transfer performed in the framework of designing a complex micro-scale cooling geometry. The numerical investigation of the three-dimensional, laminar flow (Reynolds number smaller than 480) and the solid conduction is done on a reduced model of the heat sink micro-structure to enable exploring a variety of configurations at a limited computational cost. The reduced model represents a unit-cell, and uses periodic and symmetry boundary conditions to mimic the conditions in the entire cooling manifold. A simulation of the entire heat sink micro-structure was performed to verify the unit-cell set-up, and the comparison demonstrated that the unit-cell simulations allow reducing the computational cost by two orders of magnitude while retaining accurate results. The baseline design for the unit-cell represents a configuration used in traditional electronic heat sinks, i.e. a simple channel geometry with a rectangular cross section, with a diameter of 50 μm, where the fluid flows between two cooling fins. Subsequently three types of modified geometries with feature sizes of 50 μm were considered: baffled geometries that guide the flow towards the hotspot region, geometries where the fins are connected by crossbars, and a woodpile structure without cooling fins. Three different mass-flow rates were tested. Based on the medium mass-flow rate considered, the woodpile geometry showed the highest heat transfer coefficient with an increase of 70% compared to the baseline geometry, but at the cost of increasing the pressure drop by more than 300%. The crossbar geometries were shown to be promising configurations, with increases in the heat transfer coefficient of more than 20% for a 70% increase in pressure drop. The potential for further optimization of the crossbar configurations by adding or removing individual crossbars will be investigated in a follow up study. The results presented demonstrate the increase in performance that can be obtained by investigating a variety of designs for single phase cooling devices using unit-cell conjugate heat transfer simulations.