Coach Mike Mularkey ruled Smith out Friday, saying he had a setback with his groin injury earlier in the week.
The Jaguars also likely will be without cornerback Derek Cox. He is doubtful for Sunday's game.
With Smith sidelined, the Jaguars are expected to start Kyle Bosworth against the Vikings.
Mularkey says Bosworth "has gotten a lot of work in the preseason games. We feel confident about him going in there."