The USS Mekong was a Federation Danube-class runabout assigned to Deep Space 9 as a replacement for the USS Ganges.
In 2370, she fought the Maquis, alongside the USS Rio Grande and the USS Orinoco, near Bryma colony.
Later in 2370 it was outfitted with additional photon torpedoes and accompanied the USS Odyssey to the Gamma Quadrant to search for Benjamin Sisko after he had been taken prisoner by the Dominion.
In late 2371, Odo and Garak took the Mekong into the Unefra system when they were searching for Enabran Tain. They did find him, but were captured and taken aboard the warbird under command of Lovok and Tain. It was then carried into the Gamma Quadrant aboard the warbird. The Mekong was then destroyed while trying to escape from the Battle of the Omarion Nebula.