Newcastle Knights halfback Jake Clifford will miss next round's clash against the North Queensland Cowboys due to personal reasons, as the bottom-placed side battle with a devastating injury list early on in the season.

Clifford was subbed off last week in the Knights' horror 50-2 loss against the Melbourne Storm, with head coach Adam O'Brien stating that the halfback needs time away from the game.

"His body is OK, he has some challenges around his preparation mentally for the game," O’Brien told The Daily Telegraph.

"He is down. That’s coaching and knowing when to protect them.

"I’ll put an arm around him. He is an integral part of the team. He has some personal stuff he needs to work on off the field.

"Sunday wasn’t a great day for him. He is the first to admit that… Sometimes it’s like quicksand – it was getting worse and worse."

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Clifford joins a long injury list that has caused headaches for O'Brien, as the side will struggle to fill a 24-man squad for the Townsville trip.

"We’re banged up," O'Brien said.

"I might be dragging a few off the street to play."

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Key components of the Knights roster including Dane Gagai, Mitch Barnett, Adam Clune and Jayden Brailey are all absent from the side due to either injury or suspension, with the side not signing a replacement for scrum-half Mitchell Pearce, making it a tough period for O'Brien and his team.

The Knights will now need NRL clearance to bring in Tex Hoy into the side, whilst youngster Phoenix Crossland will look to be elevated from the bench into the starting line-up this week.

Hymel Hunt will remain on the sidelines with a knee injury, whilst Kurt Mann has been ruled out for a month after suffering an ankle injury at training last week.

Second-rower Tyson Frizell is also in doubt as he struggles to overcome an illness that saw him unable to run out the Storm game last Sunday.

"The physios are working overtime to get a few up. Tyson is still pretty crook… I’ll be stretching up at the moment," O'Brien said.

In positive news, centre Dom Young and second-rower Lachlan Fitzgibbon are both set to return from knee injuries this week, which brings a sigh of relief for O'Brien's squad heading into the next game.

The Knights sit rock bottom on the NRL ladder, having lost six consecutive games and failing to score a try in the past two games, but O'Brien is still showing faith in his side.

"We’re not going to run away," O’Brien said.

"We’re going to fight. It’s not a post-mortem. They care, they are embarrassed. I know people witnessing some of the vision they don’t care. They clearly do.

"There are standards we can’t expect. We have a reunited front. When you’re faced with adversity you run away or you fight."

The Knights travel to Townsville to face the in-form North Queensland Cowboys on Saturday night, who sit third on the ladder having won their past three games.