In the mirror universe, Doctor Leonard H. McCoy was a Human Starfleet officer who served as chief medical officer aboard the ISS Enterprise in the 2260s.

In 2266, McCoy spilled acid on a lab table in sickbay. In contrast to the primary universe, the stain was not cleaned and remained until at least another year.

In 2267, Dr. McCoy accompanied a landing party consisting of Captain James T. Kirk, Lieutenant Commander Scott, and Lieutenant Uhura to the surface of the planet Halka to demand that the Halkans hand over their dilithium crystals to the Terran Empire. When the party were beamed back to the Enterprise, an electric storm caused the party to transpose with their primary universe counterparts. However, the party were later put back into their correct reality.

In the months following Spock's assassination of Captain Kirk, McCoy became more and more suspicious of the actions that Spock was taking, such as persuading Troyius and Elas to become allies, which violated orders from the Empire. Lieutenant Commander Scott and Lieutenant Uhura shared his concerns and together they plotted to remove Spock from command of the Enterprise. However, as Uhura began to carry out their plan, she was disintegrated by the Tantalus device, and McCoy's criticisms were silenced.

McCoy eventually died in 2269/2270 of the fatal disease known as xenopolycythemia, indicating that in the mirror universe, either the Enterprise crew never encountered Yonada, or they simply destroyed the vessel.

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