The Welsh region top Pool Two after beating Grenoble 59-7 away on 9 December - a third successive bonus-point win.
"We've got to keep our focus in terms of not being complacent," warned backs coach Gruff Rees.
Wing Hanno Dirksen and Canada forward Tyler Ardron could return from injury.
Dirksen has been out since May with a knee injury, and will play in the British and Irish Cup if he does not make the senior squad.
Ardron has been missing for more than two months with a thumb injury.
"There'll be a big aspect of rotation, but a healthy share of players who played last weekend will figure again," Rees added.
"There are players who need their load to be managed, people like Alun Wyn [Jones] and Justin Tipuric get the week off and there'll probably be a couple of others."
Tipuric's absence means Sam Underhill is likely to make only his third start of the season, after missing the opening weeks with a shoulder injury.
The 20-year-old was touted as a potential England call-up if he had been fit- although coach Eddie Jones would have had to bend RFU rules about not picking players based outside England.
"It was [flattering], but you don't want to get ahead of yourself because any international call-up is a reward for performance," said Underhill.
"I think it's out of my hands, if it happens it happens and if it doesn't, it doesn't.
"[England] isn't the only option, but it's my ambition. It's where I grew up, where I played rugby as a kid. I'm an England fan, I enjoy supporting them, so that's my ambition."
Ospreys will rest Wales forwards Alun Wyn Jones and Justin Tipuric for the home European Challenge Cup game against Grenoble on Saturday.