An experimental and numerical investigation of water-cooled serpentine rectangular minichannel heat sinks (MCHS) has been performed to assess their suitability for the thermal management of gallium nitride (GaN) high-electron-mobility transistors (HEMTs) devices. A Finite Element-based conjugate heat transfer model is developed, validated experimentally and used to determine the optimal minichannel width and number of minichannels for a case with a uniform heat flux of 100 W/cm 2. The optimisation process uses a 30 point Optimal Latin Hypercubes Design of Experiments, generated from a permutation genetic algorithm, and accurate metamodels built using a Moving Least Square approach. A Pareto front is then constructed to enable the compromises available between designs with a low pressure drop and those with low thermal resistance to be explored and an appropriate minichannel width and number of minichannels to be chosen. These parameters are then used within conjugate heat transfer models of a serpentine MCHS with silicon, silicon carbide, diamond and graphene heat spreaders placed above a GaN HEMT heating source of area 4.8 × 0.8 mm 2 , generating 1823 W/cm 2. A nanocrystalline diamond (NCD) layer with thickness of 2 µm is mounted on the top surface of the GaN HEMT to function as a heat spreader to mitigate the hot spots. The effect of volumetric flow rate and heat spreader thickness on the chip temperature has been investigated numerically and each of these has been shown to be influential. For example, at a volumetric flow rate of 0.10 l/min, the maximum chip temperature can be reduced from 124.7 o C to 96.7 o C by employing a 25 µm thick graphene heat spreader attached to the serpentine MCHS together with a NCD layer compared with a serpentine MCHS without these heat spreaders.