Recent advances in spherical nanoindentation protocols have proven very useful for capturing the grain-scale mechanical response of different metals. This is achieved by converting the load-displacement response into an effective indentation stress-strain response which reveals latent information such as the elastic-plastic transition or indentation yield strength and work-hardening behavior and subsequently correlating the response with the material structure (e.g., crystal orientation) at the indentation site. Using these protocols, we systematically study and quantify the microscale mechanical effects of He, W, and He + W ion irradiation on commercially pure, polycrystalline tungsten. The indentation stress-strain response is correlated with the crystal orientation from electron backscatter diffraction, the defect structure from transmission electron microscopy micrographs, and the stopping range of ions in matter calculations of displacement damage and He concentration. He-implanted grains show a much higher indentation yield strength and saturation stress compared to W-ion-irradiated grains for the same displacement damage. There is also good agreement between the dispersed barrier hardening model with a barrier strength of 0.5-0.8 and void models (Bacon-Kochs-Scattergood and Osetsky-Bacon models) with the experimentally observed changes in indentation strength due to the presence of He bubbles. This finding indicates that a high density (similar to 9 x 10(23) m(-3)) and concentration (similar to 1.5 at.%) of small (similar to 1 nm diameter) He bubbles can be moderate to strong barriers to dislocation slip in tungsten.