Microchannel heat sink (MCHS) is regarded as a promising cooling scheme for high power microelectronic devices. To further enhance its cooling capacity and improve the temperature uniformity, the investigation of the MCHS employing transcritical CO 2 as coolant was conducted in this work for the first time. A three-dimensional solid–fluid conjugated model is developed to investigate the performance of CO 2 -cooled MCHS. Sufficiently changed thermophysical properties of the transcritical CO 2 is taken into account in the model. The results demonstrate that, with the same pumping power of 0.03 W, the thermal resistance ( R ) of the CO 2 -cooled MCHS is reduced by 23.34–34.62% in the inlet temperature range of 285–305 K, as compared with the water-cooled MCHS. Likewise, the maximum temperature drop (Δ T b,max ) on the bottom surface is decreased by 24.18–48.75%. The improved performance is attributed to the lower viscosity and higher specific heat of the transcritical CO 2 . Moreover, as compared with the water-cooled MCHS, R and Δ T b,max for the CO 2 -cooled MCHS exhibit a more significant reduction when the MCHS has a larger number of channels, a larger channel aspect ratio, or a smaller channel width to pitch ratio. For a given inlet pressure p in of CO 2 , the optimal inlet temperature should be appropriately lower than the pseudocritical temperature at the given p in to ensure the larger specific heat for CO 2 flowing in microchannels.