The Bengals also will be without starting quarterback Joe Burrow, who will sit out to rest his "sore" right knee and injured right pinkie for the playoffs, coach Zac Taylor said. Backup Brandon Allen is expected to get the start.
Mixon's test result came back Wednesday, sources said, and he was added to the reserve/COVID-19 list by the team. Four starters -- safety Vonn Bell, defensive end Trey Hendrickson, left guard Quinton Spain and center Trey Hopkins -- were put on the list Tuesday.
Mixon ranks second in the NFL this season with 1,205 rushing yards on 292 attempts (4.1 yard average) with 13 touchdowns, which is fourth among rushers. He also has caught 42 passes for 314 yards and three TDs.
He joined Hendrickson and rookie wide receiver Ja'Marr Chase as first-time Pro Bowl selections this season. The Bengals (10-6) clinched the AFC North title this past Sunday to secure their first playoff berth since 2015.
Burrow, who said he is healthy enough to play, expects to practice this week. He has started all 16 games this season, throwing for 4,611 yards and 34 touchdowns while completing an NFL-best 70.4% of his passes.
"Any time you can get a little break at this point in the season," said Burrow, who has been sacked 51 times this season. "You know, we played a lot of games. Bodies are starting to wear down a little bit. Rest me this week and get my body back to where it needs to be so I can get back to full strength running around the way I need to be Week 1 of the playoffs."
Taylor said it's possible that Chase also will be rested Sunday.
"I can't make a prediction on the amount of starters (who will be held out),'' Taylor said. "I can certainly say for Joe (Burrow), we'll rest him this week and make sure he's 100% ready to go. I know he's felt good and could play if needed but I just made the decision that we're going to rest him this week.''
The Bengals are in the No. 3 spot in the AFC playoff seeding, having clinched the AFC North. There are two scenarios in which they could clinch the AFC's No. 1 seed, with both requiring a victory vs. the Browns coupled with losses by the Titans and Chiefs. In addition, Cincinnati would need the Bills to beat the Jets or the Patriots to lose or tie vs. Miami.
In addition to Mixon, defensive tackle B.J. Hill was added to the reserve/COVID-19 list on Wednesday, while receiver Trenton Irwin, cornerback Trae Waynes and practice squad receiver Scotty Washington were activated off it.
"We're trying to win this game,'' Taylor said. "We need to beat Cleveland. And the guys who are going to take the field, that's what we expect from their performance and from our performance as a coaching staff.
The Associated Press contributed to this report.