Jason Taumalolo has been ruled out of the Cowboys side that will face the Knights at McDonald Jones Stadium on Saturday with a foot injury.
The mountain the Cowboys already had to climb became even steeper with news the Tonga captain will miss the match. North Queensland have won just seven of their 20 matches in 2019.
Cowboys assistant coach David Fairleigh confirmed the worst for Cowboys fans.
"He's got a foot problem, so that's extremely disappointing," Fairleigh said.
"I don't think there's anyone in the competition that can replace what Jase does for us, so that leaves a huge hole in our team and we're just going to put faith and confidence in the guys that come in and do the job."
"I have no idea how serious it is. That's one of the things the medical staff have been working overtime on to get him ready as quick as possible."
To make matters worse, Jordan McLean is no certainty to play after being a late exclusion for the game against the Broncos last Thursday.
Fairleigh said the final composition of the side probably won't be known until Friday.
"Jordan's still got a bit of an issue there. He's got to get through training and then when, and if that happens, we'll sit down and work out what the side is," he said.
Despite the run-of-outs both on the field and in the casualty ward, Fairleigh said morale among the playing group remained high.
"The boys are turning up to training with a really good attitude, good mindset, training hard, there’s no negativity around the squad whatsoever," he said.
"They understand that winning and losing is part of the game. And you've just got to keep moving on.”