Mariota left early in the second quarter of the game, and later said that his right knee was twisted during a sack by linebacker Jamie Collins.
Mariota said he wanted to return to the game, but interim head coach Mike Mularkey felt it was best to keep him out.
With Mariota out, that would leave the Titans with backup quarterback Zach Mettenberger for the rest of the season.
Mettenberger started in place of Mariota when he missed two games with a knee injury in October.
Mariota, the No. 2 pick of the 2015 NFL draft, has thrown for 2,818 yards and 19 touchdowns this season. Mettenberger has thrown for 663 yards and three touchdowns in five appearances this season.
After their 33–16 loss to the Patriots, the Titans sit in last place in the AFC South with a record of 3–11. They will play the Houston Texans (7–7) on Sunday.
- Xandria James