Jones-Drew injured his left foot on Jacksonville's opening drive and did not return to the contest. The three-time Pro Bowler went to the locker room in the first quarter and was seen using crutches on the Jaguars' sideline in the second half.
An Oakland native, the 27-year-old Jones-Drew entered the contest with a team-leading 408 rushing yards. He hurt the foot on the first play and remained on the field for one more run but couldn't come back after that.
"It felt like a little boo-boo but the second time obviously I felt it so I came out," he said. "I wanted to be out there with those guys today."
Gabbert suffered an injury to his non-throwing shoulder in the second quarter and was replaced by Chad Henne, who struggled down the stretch as the Jaguars squandered a 14-point lead in the 26-23 loss.
Gabbert had passed for 110 yards and a touchdown prior to the injury.
The Jaguars did not provide any updates on either Jones-Drew or Gabbert during the contest.
Information from The Associated Press was used in this report.