The selection of material for compact plate heat exchangers (CPHEs) is of increasing importance due to global economic and supply constraints. Additionally, the influence of material selection on the thermo-hydraulic characteristics of CPHEs is an area of ongoing research. This study aims to address these issues by analyzing the thermo-hydraulic performance of CPHEs made from steel, aluminum, and titanium materials with small, complex channels. Using an additive manufacturing method (specifically Direct Metal Laser Sintering), lung-inspired CPHEs of identical geometry and roughness were manufactured from steel, aluminum and titanium powders. The thermo-hydraulic characteristics of CPHEs as well as that of a traditional one with Chevron-type, were investigated using both experimental and numerical techniques under specific operating conditions to determine the optimum between maximum heat transfer and minimum pressure drop. The findings of this study reveal that as the temperature difference between the inlet on the hot and cold sides, as well as the flow rate, were increased, there was a corresponding increase in both amount of heat transferred and loss of pressure across all investigated CPHEs. Compared to the chevron type brazed plate heat exchanger, the CPHE made from aluminum showed a 75.2 % and 11.2 % increase in heat transfer and a 31.8 % and 10.9 % reduction in pressure drop at 3 and 6 L/min, respectively, for a temperature difference of 90–40 °C. This study suggests that the use of materials with different thermal conductivities in CPHEs may offer a promising solution to achieve elevated heat transfer rates while minimizing pressure drop.