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The USS Cairo was a Federation Excelsior-class starship operated by Starfleet during the 24th century.

In 2369, it was under the command of Captain Edward Jellico, who was temporarily transferred to command the USS Enterprise-D for a special diplomatic mission to the Cardassian border. (TNG: "Chain Of Command, Part I")

Shortly thereafter, the Cairo was deployed to defend the Federation system Minos Korva when it was threatened by a potential Cardassian attack. Following the peaceful conclusion of the crisis, Captain Jellico returned to his command on the Cairo. (TNG: "Chain Of Command, Part II")

During the Dominion War, the Cairo was commanded by Captain Leslie Wong, and assigned to patrol the Romulan Neutral Zone in 2374. The ship was believed to have been ambushed and destroyed by Dominion forces who had crossed Romulan space to attack the Cairo. (DS9: "In the Pale Moonlight")

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The Star Trek Encyclopedia (4th ed., vol. 2, p. 327) listed the Cairo with the registry NCC-42136. In the Star Trek Encyclopedia (3rd ed., p. 471), the Cairo was identified as an unnamed Excelsior-class starship that appeared in "Preemptive Strike". This information was omitted from the fourth edition. For the sake of continuity, this article assumes that the USS Gorkon, not the Cairo, remained Nechayev's flagship following the Borg incursion.

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