In the present study, two nanofluids namely Multi-walled carbon nanotubes and Titanium dioxide dispersed in distilled water, have been used with three different concentrations; 0.1%, 0.2%, and 0.3% by volume, to investigate heat transfer enhancement in spray cooling applications. A square copper specimen of 10 mm2has been spray cooled with a volumetric flux of 2.5 cm3/cm2s using a 0.4 mm diameter pressure nozzle. The results revealed that the average heat transfer coefficient and corresponding critical heat flux enhanced significantly at 0.2 vol% for both nanofluids in contrast to distilled water. The results showed an improvement of 21.9% and 26.3% in heat transfer coefficient for Multi-walled carbon nanotubes and Titanium dioxide nanofluid, respectively. The effect of hybrid nanofluid in various concentrations has also been investigated on heat transfer performance. The results obtained showed a maximum value of 425 W/cm2for critical heat flux and 4.42 W/cm2K for heat transfer coefficient, with a heat transfer coefficient improvement of nearly 40.31% in comparison to distilled water. This results in an enhancement ratio of 1.6 for critical heat flux and 1.4 for heat transfer coefficient. In contrast to single nanoparticle nanofluid, the hybrid nanofluid indicated a moderate improvement in heat transfer coefficient of 11.7% and 7.8% for Multi-walled carbon nanotube and Titanium dioxide nanofluids, respectively. It has been observed that heat transfer performance was first enhanced and then declined as the volume fraction increased from 0.1% to 0.3% for all the nanofluids.