Manly will need to overcome a grim statistic to defeat Brisbane, with the Sea Eagles winless when they are without both Tom Trbojevic and Jason Saab.

Coach Anthony Seibold confirmed on Friday morning illness had forced Saab into a casualty ward also featuring Trbojevic (quad), Siua Taukeiaho (calf), Jake Trbojevic (concussion) and Taniela Paseka (Achilles).

The Sea Eagles will wait until game day to determine whether captain Daly Cherry-Evans backs up from State of Origin duty on Saturday night, with Jake Arthur on stand-by to play halfback.

Manly have lost all nine games when both Saab and Trbojevic have not played since winger Saab's arrival from St George Illawarra in 2021, most recently falling to Cronulla in round six.

They lost to Saturday night's opponent Brisbane without the duo last season before falling to the Sharks in a big round-27 loss.

Trbojevic and Saab offer creative flair and pace out wide, the ability to start sets strongly out of yardage and are both aerial targets for Cherry-Evans' kicks close to the tryline.

Clayton Faulalo looks set to replace Saab after originally being listed as 18th player for ninth-placed Manly.

"We've had a bit of illness go around the group. Unfortunately we lost Benny Trbojevic to illness last week and we've lost Saaby to illness this week," Seibold said.

Veteran forward Jake Trbojevic is tracking to return from an extended concussion lay-off to face Newcastle next Thursday and will likely be joined by Saab and Taukeiaho.

The Broncos game may be the only one Tom Trbojevic misses, with the fullback set to take on light duties at Friday's captain's run as Seibold downplays his latest injury.

"If it was a Sunday game (next weekend), it'd be 100 per cent certain that he'd play (against the Knights)," Seibold said.

Seibold admitted it had been frustrating for Trbojevic that short-term injuries had impacted his availability for a hot-and-cold Manly side desperately in need of his guidance.

The clash with Brisbane looms as especially crucial as Manly hope to bounce back from a demoralising loss to depleted cellar-dwellers Parramatta last week.

"As important as this game is, we're not even halfway through the season yet. That's why we've been conservative with Turbo," Seibold said.

"(The injuries) are frustrating for him because he's such a good pro.

"This is the most minor injury or niggle but we need to look after him."

Seibold heaped praise on Trbojevic's understudy Lehi Hopoate, who has lined up at fullback four times already this season.

"We're a better side with 'Turbo' in, there's no doubt about that. But Lehi's been our most consistent player all season," Seibold said.

"Whenever we've moved Lehi to fullback, he's done a really good job."