He was named in Warren Gatland's side to face Australia on December 1, but failed to shake off the injury and has now been ruled out for up to two months.
"Ian has been troubled by an ongoing problem with his right knee since being unable to complete the Samoa game last month," said Ospreys head physio Chris Towers.
"Investigations and consultations with specialists have resulted in him undergoing a keyhole procedure, as a result of which he will be sidelines for six to eight weeks."
If sidelined for eight weeks, Evans could return for the LV=Cup clash with Newport Gwent Dragons.
But that would leave the 25-cap second-row desperately short of game time ahead of Wales' Championship kick-off with Ireland the following week.
He will definitely miss the Ospreys' back-to-back Heineken Cup clashes with Toulouse, which kick-off at Stade Ernest Wallon tomorrow.
Fellow Welsh internationals Alun Wyn Jones, Jonathan Thomas, Adam Jones, Aaron Jarvis, Richard Hibbard and Ian Evans have also been ruled out of the clash.
But Dan Biggar and Ryan Jones return to the region, who hand a debut to their new signing, ex-All Black, Campbell Johnstone.
Jonathan Humphreys admits the injury list is a concern but he has urged his side to take on their underdogs tag and bite back,
"To go an take on someone like Toulouse at their ground is one of the toughest asks in European rugby, particularly when we have such a long injury list," said Humphreys.
"We are up against one of the strongest squads in the competition with a budget that you can't compare to ours, and we know that we are going to have to be at our very best if we hope to get anything out of the game whatsoever.
"What I would say though is that we have a great spirit in this group, a real togetherness, and we will go out there believing in our own ability rather than focusing on what Toulouse are about.
"We are going to have to give probably our best ever display as an Ospreys team if we are going to bring anything back from Toulouse but one thing you can guarantee is that we will give it absolutely everything.
"The Ospreys spirit is about fighting for the cause, giving everything and never knowing when we are beaten, and that is what you can expect at the weekend.
"We realise that we are going into the game as underdogs but that's a good place for us to be.
"We're looking forward to it, we know that there'll be Ospreys fans traveling out to support the cause like they always do, and we want to put in the kind of performance that will make them proud of their team."