The Marlins won 7-1, and the right-hander dropped to 10-2 in 12 home starts this season after allowing five runs and seven hits.
Eflin was hurt while attempting to field Garrett Hampson's bunt single leading off the fourth and will undergo tests.
"It just kind of grabbed him," Tampa Bay manager Kevin Cash said. "I think his cleat got caught a little bit. Don't know much more."
Eflin signed a $40 million, three-year contract during the offseason that was the largest deal for a free agent in Tampa Bay history. He was bidding to become the American League's first 12-game winner.
The 29-year-old has a history of knee problems.
Eflin began last season in the Philadelphia Phillies' rotation but made his last start on June 25 and was sidelined by right knee soreness. He returned on Sept. 14 and made seven appearances out of the bullpen with a 1.17 ERA, then had a 3.38 ERA over 10 2/3 innings in 10 postseason relief outings.
Eflin's 2021 season was cut short by a torn patellar tendon in his right knee that required surgery. He had surgery on both knees in 2016.
Tampa Bay has starting pitchers Jeffrey Springs (Tommy John surgery), Drew Rasmussen (elbow ligament internal brace surgery), Josh Fleming (left elbow inflammation) and Shane Baz (Tommy John surgery) on the injured list.
The Associated Press contributed to this report.