The mechanical properties of “cold” rolled tungsten sheet after neutron irradiation at high temperature are investigated by instrumented indentation and crystal plasticity finite element modelling (CPFEM). Neutron irradiation to a dose of 0.2 displacements per atom was performed in the temperature range from 600 to 1200 °C in the Belgian material test reactor BR2 at SCK CEN, Mol. The contribution of the irradiation damage in the constitutive laws has been deduced by utilizing the load-depth curves of the indentation measurements and incorporating microstructural information from transmission electron microscopy measurements. The simulated load-depth curves are in very good agreement with the experimental data indicating that the model can characterize the plastic deformation of the irradiated W material. It is found that the irradiation temperature has almost no effect on the load-depth curves and the hardness increase, of around 19% after irradiation, is temperature independent within errors. The formation of voids after irradiation is the main cause of irradiation induced hardening while the dislocation loops have a much lower influence. Indentation tests at low and high loading rates showed that the void dominated microstructure is more sensitive to the increase of the deformation rate.