The Penrith Panthers have been ravaged by a double injury blow, it was announced on Tuesday afternoon.

Just hours before team lists drop for their clash against the Storm, the Panthers provided an update stating both Tyrone May and State of Origin representative Brian To'o will miss significant chunks of time.

The statement confirms To'o picked up an ankle injury against the Broncos last weekend, and scans have now confirmed it's a syndesmosis injury.

The star winger, who runs for more metres than any other player in the competition, will miss up to six weeks. It's understood the surgery will be to assess and potentially repair the damage.

Syndesmosis injuries generally range in the six to eight-week recovery range, meaning To'o will almost certainly miss the remainder of the regular season with just six weeks to go.

May, on the other hand, suffered a medial ligament injury in his left knee during the opening minutes of their clash against Brisbane.

AUCKLAND, NEW ZEALAND - AUGUST 24: Tyrone May of the Panthers in action during the round 24 NRL match between the New Zealand Warriors and the Penrith Panthers at Mt Smart Stadium on August 24, 2018 in Auckland, New Zealand. (Photo by Anthony Au-Yeung/Getty Images)

The club statement didn't confirm how long May will be out for, however, mentioned that he will be missing for an "extended period."

May, who has been in the halves in recent weeks, will likely be replaced by Matt Burton, who played in the centres during Penrith's win over Brisbane on Saturday.

That is as the side continue to wait on Nathan Cleary, who is said to be likely to return from the Round 21 clash against the Sydney Roosters.

It means this weekend's blockbuster clash with the Storm will see Penrith missing Cleary, May and To'o, as well as Isaah Yeo, who is out with a concussion, and James Fisher-Harris, who has returned to Sydney for the time being, while Apisai Koroisau is also out, serving a suspension for breaching the NRL's COVID bubble when in State of Origin camp.