Head coach Brandon Staley clarified Friday that Ekeler, who has not practiced all week, has an ankle sprain but didn't divulge much more.
Ekeler tallied 117 yards and a touchdown on the ground in his team's Week 1 loss to the Miami Dolphins, but did not come away unscathed and is poised to miss Sunday after playing in all 17 games last season. Should Ekeler be inactive, it's likely Joshua Kelley will see a starter's share of the reps.
Bosa also played in the season opener, but will be a game-time decision, per Staley.
Ekeler has racked up 38 total touchdowns over his past two seasons. Bosa, who posted double-digit-sack seasons in four of his first six years, missed 12 regular-season games a year ago due to injury.
There's a chance the Bolts could be without some serious firepower on both sides of the ball Sunday.