Neither Tashaun Gipson nor Joe Haden practiced for the third consecutive day Friday and both Pro Bowl defensive backs were ruled out for Sunday's game against the Broncos.
This will mark the second straight game missed by Gipson (ankle) and the second time this season Haden (concussion) has been sidelined with an injury.
Linebacker Craig Robertson (ankle) also will miss his third consecutive game.
"That's tough to have two guys that are Pro Bowl guys that are not out there for you," Browns coach Mike Pettine said. "We're confident in the depth in the room and we've gotten a lot of quality reps with those guys."
Jordan Poyer, who received a game ball for his performance in Gipson's spot last week, will continue to fill the void at safety while Pierre Desir appears poised to once again step up for an injured cornerback.
"For me, I just prepare like I'm the starter. Whether it's Joe's position or (Tramon Williams') position, I need to know what they're both doing," Desir said earlier this week. "If I do get in the game, I'm not left behind or not knowing what's going on."
The Browns are facing a Denver passing attack that ranks 23rd in the NFL, but has no shortage of playmakers. Demaryius Thomas is 6-foot-3, 229 pounds and coming off a 1,619-yard 2014 season. Emmanuel Sanders is a similar threat and is among the NFL's leaders in receptions (34).
Denver, of course, is quarterbacked by future Hall of Famer Peyton Manning.
"With (Haden and Gipson), it would have been a challenge and it will still be a challenge now," veteran defensive back Tramon Williams said. "We know that, so we just have to play good team ball and hopefully we give a good showing for the fans."
Defensive end Desmond Bryant (shoulder), running back Isaiah Crowell (toe), wide receiver Marlon Moore (hamstring) and linebacker Karlos Dansby (foot) are considered questionable for Sunday's game. Quarterback Josh McCown (ankle) is among those considered probable.