Heat exchangers are major components that significantly influence the performance and size of industrial processes. Supercritical CO2 (sCO2) is a highly promising working fluid for various applications due to its potential to reduce equipment size, lower environmental impact, and enhance performance. The properties of CO2 near the critical point exhibit significant variations, making it particularly favorable for heat transfer. As part of the Horizon 2020 DESOLINATION (DEmonstration of concentrated SOLar power coupled wIth advaNced desAlinaTion system in the gulf regION) project, a printed circuit heat exchanger (PCHE) for an sCO2 power cycle was designed, additive manufactured, and tested. Computational fluid dynamics (CFD) simulations using the SST k–ω turbulence model and real-gas equation of state were used to analyze the heat transfer performance and friction losses of the PCHE in detail. By combining experimental measurements with numerical simulations, this study provides a comprehensive evaluation of the thermo-hydraulic performance of sCO2 near the pseudo-critical region under various operating conditions (73.78 < p < 92.32 bar, 307.02 <T_b < 334.74 K, 1823 < G < 4064 kg/m2s). A new friction factor correlation, derived from experimental data, is proposed to enhance the accuracy of friction loss predictions for sCO2 flows in microchannels, with errors within ±10%. The findings highlight the superior heat transfer performance of PCHEs while addressing the challenges associated with their performance prediction due to steep fluid property gradients in the supercritical region.