Linebackers Daiyan Henley, Eric Hendricks and Chris Rumph II were also listed as doubtful for the game, each with a hamstring injury.
Ekeler sustained an ankle injury during the Chargers' Week 1 loss to the Miami Dolphins. He missed practice Wednesday, Thursday and Friday.
Bosa, however, returned to practice in a limited capacity Friday after missing the previous two sessions.
Ekeler, 28, joined the Chargers in 2017 and has 3,844 yards and 35 touchdowns on the ground as well as 393 receptions for 3,495 yards and 29 scores. He has scored 39 touchdowns (26 rushing, 13 receiving) since the start of the 2021 season.
Bosa, 28, a four-time Pro Bowler, has 60.5 career sacks in 85 games (80 starts) for the Chargers, dating back to the 2016 season when the franchise was located in San Diego.
The Titans ruled out cornerback Kristian Fulton (hamstring), who was limited in practice all week, and safety Amani Hooker (concussion), who has not practiced. Wide receiver DeAndre Hopkins (ankle) is questionable, as is rookie offensive lineman Peter Skoronski, who popped up on Friday's injury report with an illness.
—Field Level Media