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Cowboys fullback Valentine Holmes.

Valentine Holmes will be one of three Cowboys debutants as North Queensland prepares for both a cyclone and a blockbuster derby on Friday night.

The man Holmes replaces at fullback, Scott Drinkwater, will start in the halves after winning his battle with Jake Clifford for the No.6 jersey.

Holmes, who sat out the 2019 NRL season after chasing an NFL career, will be joined by Esan Marsters (Tigers) and Reece Robson (Dragons) in making their club debuts.

A sellout crowd at the new Queensland Country Bank Stadium could experience monsoonal conditions as Tropical Cyclone Gretel threatens to make landfall around the same time as the match.

Cowboys coach Paul Green said he was not concerned about the wet weather, but admitted that selection was no easy task.

"There were a couple of tough decisions we had to make," he said.

"One of the areas we looked at last year was strengthening some positions where we lacked a bit of depth.

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"I'm comfortable and happy with where we are at."

Green said Drinkwater's pre-season form and consistency gave him the nod over Clifford, despite the fact Drinkwater missed the last trial against the Storm.

"He was probably playing with a little bit more confidence," the coach said.

"His form throughout the trial period and the Nines was a little bit more consistent."

Green said Clifford would remain in calculations throughout the season.

"I'd like to see Jake react in a good way. It's tough for him, he's obviously pretty disappointed and understandably. 

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"If he can just be a bit more consistent with his best footy he can put his best foot forward and challenge them [Drinkwater and Michael Morgan]."

Tom Opacic was another noticeable exclusion from the Cowboys side after a strong 2019 season.

Green instead opted for the experience of premiership centre Justin O'Neill, who will partner up with Kyle Feldt on the right side.

O'Neill returns to field after a life-threatening injury he sustained in May last year.

He spent four days in intensive care after emergency surgery in Canberra, which included three blood transfusions.

"I'm just excited to get back playing some footy again," O'Neill said on Tuesday.

"It's been a long pre-season and I guess getting older you can feel it a bit more."

Green said it was a difficult call to leave out Opacic and play Ben Hampton and Marsters on the left side.

"Tommy had a pretty good pre-season. It's more about bringing Justin O'Neill closer to the ball," he said.

"(O'Neill's) trial form has been really good. He makes us more dangerous and having Ben Hampton in the team gives us utility value.

"A head knock or a SCAT test can really upset your team. This means we've got all bases covered."