Trbojevic suffered his sixth hamstring injury in as many years in Thursday night's 30-24 loss to the Dolphins, before limping off Suncorp Stadium.
The Sea Eagles are yet to receive the results of scans as the remainder of the team head north to a Sunshine Coast base ahead of Magic Round.
But the club believe the fullback has suffered a grade-two tear, which would rule him out for between six and eight weeks.
Winger Jason Saab is also expected to be sidelined for up to four weeks with an AC joint sprain, with the good news being there is no dislocation in the shoulder.
The timing is at least not a disaster for Manly.
If Trbojevic was to return in early July, he would only miss five matches given Manly have a bye in that period.
But that would mean missing games against Penrith and South Sydney during NSW Origin preparation and recovery.
Trbojevic was injured trying to stop a flying score from Dolphins winger Jack Bostock. (Dave Hunt/AAP PHOTOS)
Still, his absence is a hammer blow to Manly's season.
The Sea Eagles remain a far better team with him on the field, winning 63 per cent of 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, and in turn reducing the need to call in both Paulo and Tuaimalo Vaega.
Trbojevic's injury means he will also likely miss the first two Origins for NSW, and face an uphill battle to reclaim his centre spot for Game 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.
At Manly, they know they must 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 one 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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