The Jefferson Motel is a motel located in Jefferson, Los Santos; and is the main setting of Reuniting the Families. The motel has a number of rooms and a Sprunk vending machine, allowing the player to replenish Carl Johnson's health (at any point of the game). The motel is the meeting place for the Grove Street Families, Seville Boulevard Families and Temple Drive Families in Reuniting the Families. The meeting, aimed at re-uniting the families, is ambushed by the police. The southern wall of the motel also has a gang tag that can be sprayed, there is also an MP5 on the roof of the hotel. Jefferson, the district the motel is in, is controlled by the Ballas in 1992 , although not many Ballas patrol the Jefferson Motel, which makes it harder to take over.
- In GTA: The Lost and Damned during the mission Shifting Weight the character Malc makes reference to the Jefferson Motel, joking that they should go the Jefferson Motel for some light bondage.
- There is a hidden save point in the hotel in San Andreas in a skylight in the 2nd lobby (the one with the knocked down table) of the hotel. If you go next to the chair against the wall near the corridor you can see it if you look up. The save icon is not accesible using the spawn jetpack cheat due to the fact that the jetpack doesn't work in the motel.