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The Federation starship USS Cairo (NCC-42136) was an Excelsior-class Federation starship in service in the 24th century.

In 2367, 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") The Cairo was deployed to defend the Federation colony on 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 in 2374, the Cairo was commanded by Captain Leslie Wong, and assigned to patrol the Romulan Neutral Zone. It was ambushed by a squadron of Jem'Hadar attack ships and destroyed with the loss of its entire crew. (DS9: "In the Pale Moonlight")

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