The current paper focuses on the issue associated with the biological response of medical grade cobalt chromium (Co–Cr) alloy treated with electrical discharge at different spark energy levels by a varying current, pulse on-time, and pause (off) time. Three types of electrodes, namely, graphite (C), tungsten (W), and copper tungsten (Cu–W) were utilized for treating Co–Cr substrates in two different dielectric media such as mineral oil and deionized water. Electrochemical potentiodynamic tests were performed to investigate the corrosion resistance of untreated and treated surfaces. Furthermore, in vitro hemocompatibility tests were executed on the superior corrosion resistance samples for scrutinizing the red blood cell lysis (human blood response). The study revealed a significant improvement in the corrosion resistivity (<80%) and biological response for the surface treated with W–Cu electrode at low pulse pause duration. X-ray diffraction verified the formation of oxides and phosphides on the treated surface that promotes the biocompatibility.