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Capain Jacob Keyes served aboard this vessel prior to 2535, and he was awarded the Medal of Honor for his efforts in defending the vessel against an overwhelming Covenant attack force with only a small security force. It is unknown if it is still in service.
- The Meriwether Lewis is named after the famous explorer of the same name who, along with William Clark, mapped out most of the Western United States in the early 1800s.
- In the Halo: Combat Evolved manual, this ship was classified as a Colony Ship. For more information see: List of inconsistencies in Halo.
- Halo: Combat Evolved manual (Mentioned only)
- Halo: The Fall of Reach (Mentioned only)
- Halo: The Cole Protocol (First appearance)