The thermal and hydraulic performance of single-phase water-based alumina nanofluids used as coolants in liquid-cooled cold plates are reported and results baselined against those using water. Experimental results show that the heat transfer coefficient of the nanofluids increases with increasing particle loading at a fixed Reynolds number. When compared on the basis of a fixed volumetric coolant flowrate, pressure drop, and pumping power, however, no significant enhancements were observed using dilute (2%, 4%, and 6% volume fraction) alumina–water nanofluids (having an average diameter of 50 nm). In some cases, the thermal performance using nanofluids deteriorated. These results suggest that water-based alumina nanofluids do not offer a significant benefit for single-phase cooling in cold plates for the alumina nanofluids tested; yet, there remains an opportunity to identify nanoparticles—base fluid combinations that may improve performance with suggestions made herein. It should also be noted that the results reported in this study have been obtained at different degrees of dilution of a given alumina–water nanofluid having an average particle size of 50 nm.