Trbojevic brothers Jake and Tom under an injury cloud ahead of State of Origin selections

Jake Trbojevic has been all but ruled out of the State of Origin series opener after he was knocked out in a brutal collision during Manly's clash with the Cowboys.

Trbojevic was immediately attended to by players on the field after he fell to the turf unconscious following a brutal collision with Murray Taulagi.

The Manly star had dropped the ball in a hit-up that was then swept up by Taulagi. Trbojevic attempted to rectify his error with a heavy shot on the winger when his head made contact with Taulagi's shoulders.

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His brother Tom, who was playing at fullback for Manly, was first to race over and assist the incumbent NSW skipper on the turf.

Fellow teammates and rival players also circled Trbojevic as team medics made their way to the unconscious star, with all around the area visibly distressed.

"He hit is head hard on the ground," Steve Roach said on Fox League.

"He was out on the way down... you could see straight away."

Commentator Andrew Voss added: "He's in trouble there. He is really distressed and so are his Manly teammates. Tom's the first one in there."

Trbojevic was helped by trainers off the field as the crowd raised for a standing ovation.

Trbojevic is expected to be declared a category one concussion, which mandates an 11-day stand down which would just cover Origin I.

Nathan Brown was brought on as Trbojevic's replacement when played resumed.

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Concerns about player fitness then turned to Tom Trbojevic in the second half as he appeared to be battling a lower leg injury.

The 28-year-old cautiously returned to his feet after he was tackled before he surrendered in a tack moments later.

The fullback was seen near the sidelines in what was likely a hint for coach Anthony Siebold to make a change but he was left to continue on with the battle.

Tom then bombed a near-certain try as he dropped the ball cold 10m out from the line.

"He's in all sorts," Roach said of the star fullback.

Daly Cherry-Evans also showed signs of visible discomfort late in the final 40, although managed to continue on without any assistance from team medics.

Earlier, Jason Saab darted over in the ninth minute to open the scoring for Manly.

Murray Taulagi was next to power over the line shortly after Trbojevic's departure but was denied by the Bunker as he fell short of the line.

The rejected try was not to rattle the Cowboys attack as Robert Derby levelled the scores in the 32nd minute.

Lehi Hopoate crossed for Manly's third try in the 69th minute before Ben Trbojevic burst through a hole to score the club's fourth and seal the scores at 24-6.