Cathodic Over-Protection is a critical issue that can affect the integrity and performance of prestressed wires embedded in concrete or mortar, widely used in numerous structural applications such as prestressed cylinder concrete pipes (PCCP). In this study, an experimental assessment was conducted to elucidate and evaluate the effect of Cathodic Over-Protection on most important mechanical properties and microstructures of prestressed wires under variable tensions. Over impressed cathodic protection currents were applied to six different samples of prestressed wires. Four samples were put under preset variable tensions ranging from 40% to 89% of their ultimate tensile stress (UTS), and a cathodic protection potential level of -1500 mv w/r (Ag/AgCl) half-cell, while the remaining two wire samples were put under only two preset tensions of 40% and 89% of their ultimate tensile stress (UTS), and a cathodic protection potential level of -1200 mv w/r (Ag/AgCl) half-cell. All six prestressed wire samples were immersed in a passivating alkaline environment similar to that found in mortar during the whole duration of the experiment. Results have demonstrated that for the two applied levels of cathodic over-protection, corresponding significant changes in the mechanical properties and microstructural characteristics of these wires and these observed changes were more pronounced for those samples exposed to the -1500 mv potential level. Results also showed that for the two levels of protection potential, a reduction in UTS, and hardness as tension increases, while the % area reduction at the point of failure decreases. The negative effects of Cathodic Over-Protection on the mechanical properties of prestressed wires among other possible reasons may be due to the embrittlement of wires, which may be attributed to the observed bubbling of hydrogen gas on the wire surface during the experiment. Therefore, Hydrogen embrittlement phenomenon may be a possible cause of these changes requiring further experimental investigation.