Advanced nuclear materials are one of the key factors for safe and reliable operation of future fission and fusion reactors, where they need to withstand extreme conditions. Under irradiation, creep conditions change dramatically, but the actual models cannot completely explain the experimental evidences. The goal of this study is to correlate the material response to stress and irradiation, in order to develop a new model of irradiation creep, where vacancy diffusion plays an important role. To address this point, mechanical spectroscopy tests on high-purity nickel single crystal with different lattice orientations (100), (110) and (111), were performed in a forced oscillation pendulum, under high vacuum (10⁻⁶ – 10⁻⁵ mbar), at different frequencies. The temperature range was the one of the subsequent irradiation creep tests, spanning from room temperature up to 500 °C. A periodic strain of amplitude 5x10⁻⁵ was applied. The dimensions of all the used specimens were of around 2 x 10 x 0.3 mm. The present study focuses on the understanding of the dislocation dynamics responsible for deformation, and their kinetics. The effect of different crystal lattice orientations is also studied. A general overview of the internal friction (IF) spectrum reveals three mechanical loss peaks, for all the three orientations, namely P0 (transient peak), P1 and P2. P1 and P2 might be related to a motion of dislocations controlled by the migration of two types of jogs. Activation energies of around 1.5 – 2 eV were found for both the P1 and P2 peaks. These activation energies are comparable to pipe diffusion (1.94 eV) and grain boundary diffusion (1.3 – 2 eV) in nickel. Dislocation pinned in jogs might act as grain boundaries, enhancing the diffusion of vacancy (lower activation energy compared to Ni self-diffusion (2.88 eV)). TEM analyses were performed in parallel on both as received and irradiated samples, confirming the presence of dislocation jogs and the absence of sub-grain boundaries and twins. The experiments have demonstrated that mechanical spectroscopy is a powerful tool to better understand the basic dynamics of dislocations to be compared with creep experiments conducted under irradiation conditions.