The effect of hydrogen on dislocation nucleation in a vanadium (100) single crystal has been examined by means of nanoindentation. For electrochemically doped samples to different hydrogen concentrations within the α-phase, the pop-in load decreased with the increase in hydrogen concentration and multiple pop-ins were observed on the load–displacement curves. The interaction between the dissolved hydrogen atoms and the newly formed dislocation loops, resulting in the reduction of their line energy, is evaluated and explained based on the novel thermodynamic defactant concept.