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

The Cairo was dispatched from Starbase 11 to defend the Planet Q colony from Cardassian attack in 2351. With other Starfleet and Klingon ships, the Cairo successfully drove the Cardassian attackers away. (Star Trek: Pendragon)

In 2369, the Cairo was under Captain Edward Jellico's command until he temporarily took command of the Enterprise-D. The Cairo defended the Federation system Minos Korva when the Cardassians planned to attack it. Jellico returned to command the Cairo once the crisis was peacefully resolved. (TNG: "Chain of Command, Part I", "Chain of Command, Part II")

Under the command of Captain Leslie Wong in 2374, the Cairo was destroyed while patrolling the Romulan Neutral Zone. Starfleet believed the Dominion ambushed the Cairo and destroyed it from Romulan space. (DS9: "In the Pale Moonlight")

In 2375, the Cario was rebuilt with Captain Marcus Hakim, who fought hard to have the ship keep the same registry number, as her commanding officer. (Star Trek: Pioneer; Star Trek: New Horizons: "Stranded")

In the Pendragon timeline, the Cairo was a part of Admiral James Leyton's fleet during Operation Return.

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