This work investigates the effect of high voltage (HV) electrode material of a point-plane plasma reactor on the inactivation rate of E. coli in both direct plasma and post-discharge inactivation processes. For the direct plasma processes, nickel chromium alloy, iron, tungsten and copper were used as HV electrode materials. In comparison with the other three materials, a significantly higher inactivation rate of E. coli was achieved with copper as the HV electrode. The inactivation effect was demonstrated to be mainly associated with the toxicity of copper ions, rather than from copper nanoparticles released from the electrode during the treatment. Similarly, for the post-discharge inactivation process, a higher E. coli inactivation rate was achieved in both post-plasma and plasma-treated water treatment using copper as the HV electrode, as compared to the tungsten control case. Increased inactivation rates are a result of a synergistic action between copper ions and the hydrogen peroxide generated by the plasma.