4:25 p.m. ET | CBS
Matchup rating: 56.5 | Spread: IND -2 (47)
What to watch for: Cleveland's NFL-leading running game -- now without Nick Chubb -- is up against Indy's top-five run defense. This should be a litmus tests for both sides, in a true matchup of strength against strength. -- Jake Trotter
Bold prediction: The Colts will give up 125 yards rushing. Indianapolis will keep the Browns' rushing offense in check most of the game even without linebacker Darius Leonard (groin), but they'll give up one big "chunk" run that will end up hurting them in the fourth quarter. -- Mike Wells
Stat to know: Colts receiver T.Y. Hilton has now gone 15 straight games with fewer than 100 receiving yards, dating to 2018. It's the longest streak of his career, and his last game with 100-plus yards came with Andrew Luck at QB.
What to know for fantasy: Browns receiver Odell Beckham Jr.'s 38.4 PPR points last week led all receivers and ranked third across all positions. But can he sustain the success? He hasn't had consecutive 25-point games since Weeks 13-14 of the 2015 season. See Week 5 rankings.
Betting nugget: Indianapolis has had three straight games go under the total, and it has covered all three games. Read more.
Wells' pick: Browns 24, Colts 17
Trotter's pick: Browns 21, Colts 20
FPI prediction: CLE, 50.2% (by an average of 0.2 points)
Matchup must-reads: Colts' No. 1-ranked defense shifts coach Frank Reich's strategy ... Browns can still have NFL's best rushing attack -- even without Chubb ... Colts QB Rivers toes the line on friendly trash talk ... Browns' Beckham Jr. shows why he's still an elite playmaker ... Colts continue to be NFL's stingiest defense in victory over Bears ... Browns' Njoku activated off IR, could play Sunday