Thomas, 27, has snagged three passes for 17 yards this season.
The former Ohio State star suffered the high-ankle sprain in a 34-23 Week 1 win over the Tampa Bay Buccaneers.
Thomas missed just one game in his first four seasons, a 16-11 loss to the Buccaneers on Dec. 11, 2016, sitting with a foot injury.
The star has been a second-round draft steal since New Orleans took him 47th in 2016. The three-time Pro Bowler, two-time first-team All-Pro and 2019 NFL Offensive Player of the Year caught 470 passes for 5,512 yards and 32 touchdowns over his first four seasons.
He led the NFL in receptions in 2018 and 2019 and set the league record for catches in a single season with 149 in 2019. Thomas also paced all players with 1,725 receiving yards last year.
Without Thomas, expect the team to rely more on No. 2 wideout Emmanuel Sanders and tight end Jared Cook. Running back Alvin Kamara could be utilized more in the passing game as well, as could wide receivers Tre'Quan Smith and Deonte Harris.
Thomas is a huge loss, especially considering that he absorbs a massive amount of passing volume (averaged 150.5 targets over his first four seasons). But the team has enough talent elsewhere to get by until he returns.