Ospreys will have more than 20 absentees when they take to the pitch at Ravenhill with Dan Biggar, Richard Hibbard, Adam Jones, Ian Evans, Ryan Jones and Justin Tipuric on international duty.
Ulster are unbeaten at home in the RaboDirect Pro12 this season and have only lost once in the competition so far to sit top of the ladder while Ospreys are just inside the play-off places in fourth.
However Ospreys have enjoyed success at Ravenhill in recent seasons beating Ulster 16-13 in 2009 and 38-27 in 2010 and only losing by a single point on their last two visits.
And, despite effectively being unable to call upon an entire squad as the RaboDirect Pro12 returns, Humphreys insists those that are left won't go down lightly.
"We've got more than 20 boys unavailable because of internationals and injuries," he said. "We're being really tested with the strength of our squad and we know this period is vital to us.
"They're really passionate at Ravenhill but it's somewhere where we've had success before. We've gone out there and won in trying circumstances, and this will be no different.
"We understand the task that's in front of us. It's going to be a huge ask for a lot of our players. We're going to be playing boys out of position, especially in the backline where we'll have a scrum-half on the wing - simply because we don't have anyone else there.
"These boys are doing a fantastic job but it will be a huge ask for them. It's a very vocal crowd but when you're on the field you don't really take notice of it."
The RaboDirect Pro12 returns for the first time since January 5 as the Heineken Cup and LV= Cup took precedence with Alun Wyn Jones expected to return for Ospreys.
The 27-year-old second row damaged his shoulder during Wales' defeat to Argentina in November while Ryan Bevington and James King have been released back to their club.
Fly-half Stuart Olding will make his first start for Ulster while Johann Muller has returned from injury, alongside Luke Marshall, and will skipper the team.
Prop Andrew Warwick could make his senior debut after being named on the bench and Ulster coach Mark Anscombe couldn't be happier for him.
"Andrew has worked hard and has done well with the Ravens and this presents an opportunity for him to be part of the squad," said Anscombe.
"It also presents an opportunity for us to see him in the environment as well, so it is good for everyone."
At Ravenhill , 7.05pm.
Referee: Marius Mitrea (FIR, 15th competition game) Live on
Assistant Referees: Paul Haycock, Nigel Correll (both IRFU)
Citing Commissioner: Peter Ferguson (IRFU)
TMO: Simon McDowell (IRFU)
Live on BBC NI and BBC Wales