Thomas has played a key role in a prolific Oregon offense that has scored at least 50 points in four straight games for the first time in school history. He's paced the nation's top rushing attack (332.5 yards per game) with 338 yards and six touchdowns on 42 carries for the Ducks (4-0, 1-0 Pac-12).
The speedy junior, however, slipped and clutched his lower right leg during the opening kickoff in Saturday's 55-16 win over California in a rain-soaked Pac-12 opener. After the half, he appeared on the sidelines with crutches and left practice Tuesday wearing a boot on his injured right ankle.
Running backs coach Gary Campbell told reporters on Tuesday that Thomas' return is "not going to happen" against the Buffaloes (2-1, 0-1).
"The type of player he is, you're going to miss him no matter what, but guys really stepped up - Byron (Marshall) stepped up and Thomas (Tyner) stepped up," Mariota told Oregon's official website. "The motto around here is 'next man up.' Those guys played well, and obviously we're going to miss De'Anthony, but he's going to take care of it and it's his business."
Thomas rushed for 97 yards and a score on just five attempts to help the Ducks jump out to a 56-0 halftime lead en route to a 70-14 victory over visiting Colorado last October.
With Thomas out, Marshall and Tyner will see their workloads increase. Marshall filled in with a career-high 130 yards and two touchdowns against the Golden Bears, but will have to protect the ball better after fumbling three times in the wet conditions.
"We have a ton of confidence in Byron, he had an exceptional fall camp there and needs to keep developing," said Mark Helfrich, in his first season as head coach of an Oregon team that has averaged 46.3 points during its road win streak.
The Buffaloes are likely to have their hands full with Mariota, who has emerged as a Heisman Trophy candidate by throwing for 1,003 yards and nine touchdowns without an interception. He also tops the nation among all players with 14.0 yards per rushing attempt.
Mariota, who completed 10 of 14 passes for 136 yards and two scores in last year's rout, leads an Oregon team that ranks second in scoring at 59.8 points per game and third in total offense with 599.3 yards per game.
Colorado has given up the second-most points (31.7) among Pac-12 teams and allowed Oregon State's Sean Mannion to throw for 414 yards and a school-record six touchdowns in a 44-17 loss in its league opener last Saturday.
After completing 68.3 percent of his attempts for 741 yards in wins over Colorado State and Central Arkansas, Connor Wood connected on 14 of 34 passes for 146 yards with two touchdowns and two interceptions against the Beavers.
Paul Richardson was held to five catches for 70 yards and a score after totaling 417 yards and four touchdowns in his first two contests.
"They're definitely a lot better (than that performance)," said Helfrich, an offensive assistant at Colorado from 2006-08. "The first couple games were a lot different; they played really, really well."
Helfrich's squad may have to keep an eye on Michael Adkins II, who provided a spark with 98 yards on 14 carries Saturday in his season debut. The freshman running back displayed an impressive burst on runs of 19 and 33 yards.
"He's fast, he gets to sidelines, he runs hard," Colorado coach Mike MacIntyre told the school's official website. "I don't know if he's the starter but he's going to play."
The Buffaloes may have a difficult time getting back on track offensively against an Oregon team that ranks fourth in the nation in scoring defense at 10.8 points per game.
Colorado also will try to contain sophomore Bralon Addison, who ran back two punts for touchdowns Saturday and leads the country with 36.5 yards per return.
Oregon has a 9-8 lead in the all-time series after winning the past two meetings by a combined 115-16.