Pendlebury failed to complete training at Olympic Park on Wednesday, leaving the track early.
The 36-year-old has been battling an arm injury since last week's draw with Fremantle.
"Pendles won't play," Collingwood coach Craig McRae told reporters immediately after Wednesday's training session.
"We anticipated he'd get through training and he'd be right, but he didn't get through training.
"We'll explore what that looks like. At this stage we're not sure, but no, he won't play.
"It's a big (blow). His leadership is critical, and with his experience he's hard to replace."
In better news for the Magpies, McRae confirmed Jeremy Howe will return from a minor groin strain to bolster their tall stocks against the Bulldogs.
Regular defender Howe started forward in Collingwood's win over West Coast in round nine before going down injured.
The versatile tall could be required in attack again, with Brody Mihocek (hamstring) and Mason Cox (concussion/knee) added to a long injury list last week.
Billy Frampton trained with the forwards on Wednesday and is another regular defender who could be swung into attack.
The Bulldogs have also been hit hard by injuries, losing key forward Aaron Naughton (knee), Ed Richards and Anthony Scott (both concussion) for the Magpies' clash.
Defender James O'Donnell is expected back from illness.