The Sea Eagles confirmed on Friday that Trbojevic had suffered a grade-two tear to his right hamstring in Thursday night's six-point loss to the Dolphins, meaning he will also miss the first two State of Origin matches for NSW.
There was better news on winger Jason Saab, who is only expected to miss a couple of weeks with a shoulder problem.
Saab was hurt trying to save a try in the first half of Manly's 30-24 defeat, but should be fit to return after the club's round-13 bye.
The timing of Trbojevic's injury is not a disaster for Manly: if the early prognosis is correct, he would only miss five matches with the Sea Eagles having two byes in that period.
The fullback was likely to have been sitting out two of those five matches if fit, as they clashed with NSW Origin camp.
Trbojevic (right) was injured trying to stop this try from Dolphins winger Jack Bostock. (Dave Hunt/AAP PHOTOS)
But the Sea Eagles remain a far better team with him on the field, winning 63 per cent of their games with him as opposed to 34 per cent without him since the start of 2019.
Centre Tolu Koula will likely deputise for Trbojevic at fullback while Jaxson Paulo and Raymond Tuaimalo Vaega are options to come into the backline.
Another possibility would be playing second-rower Ben Trbojevic at centre, reducing the need to call in both Paulo and Tuaimalo Vaega.
Tom Trbojevic's injury has serious implications for NSW, given at best he will only be fit for Origin III on July 17.
With Latrell Mitchell also unlikely to play, Stephen Crichton, Matt Burton and Zac Lomax are all possible options for new Blues coach Michael Maguire.
Manly will work hard to give Trbojevic the chance to return to a side in finals contention come July.
Haumole Olakau'atu will return from suspension against Brisbane in next Friday night's Magic Round blockbuster, alongside hooker Lachlan Croker (concussion) and forward Nathan Brown (hip flexor).
"With Saaby and Turbo (Trbojevic) going down it does put a dent in our squad but there is a group there that really care about the footy team," coach Anthony Seibold said.
"We will put a team together next week and expect to come back here and put in a better performance for longer periods.
"We have shown we are a good footy side."
Manly have had double-figure leads in all but one of their 10 games this year, but the Dolphins loss marked their fourth defeat of the season to go with five wins and a draw.
"We are in here talking about the same trend again, so it is something we need to fix and something that all of us can help each other with," captain Daly Cherry-Evans said.
"We have got to change a few things to get the result we are after. We can fix it. We just have to work harder at it."
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