Sean O'Loughlin is out of Friday's game against Hull KR - and England team-mate Joe Greenwood has joined him on the sidelines.
Captain O'Loughlin is facing a lay-off of up to four weeks with an Achilles injury suffered in the opening minute of the 28-12 win against Salford.
And Greenwood is out for an indefinite period as Wigan follow protocols for returning to the pitch after a head knock.
The backrower is to see a specialist and Lam said: "Joe is out indefinitely, we're following concussion protocols and return to play protocols.
"Until he's seen a specialist we won't know how long he may be out for, we just don't know - I'm not going to speculate on a time-frame."
O'Loughlin's absence will be a blow but Lam was thankful the injury was not more serious.
"He's got a thickening of the Achilles so there's no bad damage there, when you look at the other side, it could have been a lot worse," he said.
"I think Sean has been one of the best players in the competition for the past four weeks.
"He's an important member of our team but in saying that, we've played some good rugby without him this year and we'll get by without him. The challenge is there for some players to step up and I'm excited about seeing some of the young players."
Liam Farrell (knee) will return from a week off and Dan Sarginson's availability could move centre Chris Hankinson into the pack. Prop Ben Flower is still sidelined after tearing ligaments in his back.
"Before he was injured, Sarge was probably our best player in the two games leading up to that," said Lam, who will name a 19-man squad tomorrow.