This study using the first-principles theory investigates the geometric and electronic properties of Cu-decorated NiS2 (Cu–NiS2) monolayer, and the adsorption and sensing performance of Cu–NiS2 monolayer upon five C5F10O decomposed species, in order to explore its potential to evaluate the operation status of C5F10O-based insulation devices. It is found that the Cu atom prefers to be trapped on the H1 site of the NiS2 monolayer with the formation energy of −3.09 eV without the cluster issue. The chemisorption is determined in the Cu–NiS2/C2F6O3 with an adsorption energy of −1.05 eV, while physisorption is identified in the C3F6, CF2O, C2F6 and CF4 systems. The analyses of electronic property and recovery property reveal the strong potential of Cu–NiS2 monolayer to be a reusable C3F6 or CF2O sensor at room temperature, to be a high-sensitive and one-shot C2F6O3 sensor instead and is not suitable for C2F6 and CF4 sensing due to the low sensitivity. This work is meaningful in terms of proposing novel sensing material for application in the power system to ensure the good operation of C5F10O-based insulation devices. Research Highlights Cu-decorating behaviours on a pristine NiS2 monolayer are studied. The sensing mechanisms of Cu–NiS2 monolayer upon five C5F10O decomposed species are expounded. The sensing potential of Cu–NiS2 monolayer as a resistance-type gas sensor is explored.