Etienne will undergo surgery for a Lisfranc injury, a league source told ESPN's Adam Schefter.
The running back suffered the injury to his left foot in Monday's 23-21 loss at the New Orleans Saints. Tests on Tuesday showed the extent of the damage.
Etienne caught one pass for 3 yards and carried the ball once for 1 yard before getting hurt. Because he was placed on IR before making the initial 53-man roster, Etienne will not be allowed to return this season.
The Jaguars drafted Etienne 25th overall in the 2021 draft.
Coach Urban Meyer said he planned on having Etienne line up at receiver in addition to running back, similar to the way he used Percy Harvin at Florida. However, Etienne had only one carry in the preseason opener against the Cleveland Browns, although he was open in the flat for what could have been a big play if quarterback Gardner Minshew hadn't overthrown him.
Meyer said he hoped Etienne would bring a big-play element to the offense. The Jaguars were last in the NFL in combined rushes of 20 or more yards and pass plays of 30 or more yards, per ESPN Stats & Information. They had 16, which was 33 fewer than the league-leading Baltimore Ravens.
Etienne was one of the most explosive players in the country over the past four years. He led all players in college football with 55 runs of 20 or more yards from 2017 to 2020, rushing for 2,053 yards and 21 touchdowns -- an average of 37.3 yards per carry on those big plays.
Etienne also had six receptions of 30 or more yards, giving him 61 explosive plays. For comparison, the Jaguars had 97 explosive plays from 2017 to 2020. The Kansas City Chiefs led the NFL with 173, and the only four teams that didn't have at least 100 (the Jaguars, Cincinnati Bengals, Miami Dolphins and New York Jets) all had losing records during that span. The Jaguars also averaged 19.5 points per game in those four seasons, fewer than all but five teams.
Etienne left Clemson as the ACC's all-time leading rusher (4,752 yards).