Tom Trbojevic will miss only two weeks however Kelepi Tanginoa and Curtis Sironen have been ruled out for the season in a devastating blow for Manly.
Trbojevic set up four tries for the Sea Eagles and scored one of his own before limping off during their 32-16 NRL win over Canberra on Saturday night.
The 21-year-old has previously had surgery on the same ankle at the end of 2016 and the club said on Sunday he would miss the side's upcoming clashes with the Gold Coast and Wests Tigers.
But that's as good as the news got for the under-siege Sea Eagles with Sironen (ruptured ACL) and Tanginoa (ruptrued MCL and ACL) set to miss the rest of 2018.
It puts a massive dent in Manly's forward stocks and will likely see Darcy Lussick and Frank Winterstein recalled.
"Both players worked extremely hard in the pre-season and have been very good for us in the first four weeks of the competition,'' coach Trent Barrett said.
"We all feel for them. Kelepi and Curtis will have the club's full support.
"It is a big blow to the side but we have plenty of good depth in the forwards, so we will fight on."
Still, it was the Raiders who left Lottoland with a bigger headache after Ricky Stuart labelled their performance "soft" as part of their worst start to a season in 21 years.