Wheeler, who has played every game for the Highlanders this season, has suffered a serious injury to the medial ligament in his knee.
He was seeing a surgeon about the injury yesterday, Highlanders coach Jamie Joseph said.
Wheeler (27) was out for six to eight weeks and possibly longer.
''He [Wheeler] has got quite a nasty knee injury. That is a real blow to us,'' Joseph said.
''It does not look very good, to be fair. His MRI scan suggested he would be out for the rest of the season.
''He has been a key part of the team in the past two or three seasons and has been playing really good football. He is one of our senior players. A funny guy, too, so we will miss that as well.''
Wheeler suffered the injury in the second half of the match against the Brumbies last Friday night and was forced off the field.
The Highlanders have stacked up the injuries lately, and Joseph counted 11 players out of his squad.
Wheeler's absence leaves a hole in the second row, although Mark Reddish should be back this week from a knock to his ankle. Alex Ainley is still getting over a broken jaw picked up in a club game.
Joseph said the injury situation was worse than normal and not helped by players in the same position getting banged up.
''We have had some serious injuries. Unfortunately, they are in the same position, locks and props. If you can distribute those whole injuries over the whole group of 39, then it would not be so bad.
''But when they are targeting in one or two positions, then they are costly for the team.
''It is always disruptive to the team when you get so many injuries. Joe has played in every game for us this year and he is a big loss to the team ... and as we get into the business end of the season.''
No one has been brought into the squad to replace Wheeler.
Midfield back Shaun Treeby rolled his ankle in the loss to the Brumbies and is unlikely to front this week.
Long term casualties Shane Christie and John Hardie are back training, as is prop Ross Geldenhuys.
The Highlanders head to South Africa on Sunday and will be taking a squad of 27.
Meanwhile, the Highlanders have done a deal for a bonus free Zoo stand opening tomorrow night.
Originally, the franchise had decided to not open the western end of the stadium, as a Friday night game against a South African side was not usually a big draw.
However, Vodafone X got on board and has bought 4000 tickets for the game. Tertiary students will get free access to the stand provided they carry out a Vodafone promotion and have a current student identification.
