Molloy will need back surgery, ending her season, in a major blow for the Swans.
Sydney's season is on the brink heading into the final round. They are ninth and will play 15th-placed Essendon on Saturday in Coffs Harbour.
Coach Scott Gowans is hopeful of recalling Sofia Hurley from injury. He added Cynthia Hamilton's nasty-looking knee and ankle injury last weekend was not as bad as first feared.
But after needing back surgery in 2023 and having most of last year's season ruined by a knee reconstruction, Molloy is out of action again.Â
"We really won't know any more ... until the surgery's done," Gowans said on Tuesday.
"It's similar to last time (the previous back surgery), but we just don't know the details.
"It's very disappointing. She's clearly one of our better players. We just have to get on with it."
The Swans revealed the huge setback in an injury update after Molloy had missed the past two games with back soreness.
One of the AFLW's best players, she had bounced back well this season after returning from her knee reconstruction.
Molloy, 26, is a three-time All-Australian. She is equal fourth in the AFLW's goalkicking this season with 19 in nine games, four behind leader Indy Tahau from Port Adelaide.
Gowans added Hamilton was still being assessed after she was injured early in Saturday's win over West Coast.
"It's not as bad as first thought - it did look really nasty. It could have been a lot worse," Gowans said.
The Swans are ninth, outside the top eight on percentage, going into Saturday's Coffs Harbour clash against 15th-placed Essendon.
Sydney are on 24 points, along with seventh-placed West Coast, eighth side Adelaide and Fremantle, who are 10th.
The Swans will start strong favourites against the Bombers, but they will also need other results to go their way to make their second finals appearance.
After winning their first four games this season, Sydney have dropped five of their past seven.
"I had a go at it myself and made myself ill," Gowans said of assessing the top-eight permutations.
"We're just clearly focused on us. We've got a little bit of a history of dropping games like this.
"This week is solely on us."