Skipper James Slipper will return home from Queensland's tour of South Africa and Argentina after suffering a ruptured Achilles tendon in the Reds' disastrous Super Rugby loss to the Lions in Johannesburg.
Star playmaker Quade Cooper could also miss next Sunday's clash with the Jaguares in Buenos Aires after being sent off in the 44-14 defeat at Ellis Park.
Cooper will front a SANZAAR judiciary hearing to answer a dangerous tackle charge after catching Lions centre Rohan Janse van Rensburg high in the 49th minute.
The Reds can ill-afford to suffer any more setbacks after sending an SOS to replacement prop Phil Kite as cover for Slipper and also watching powerhouse centre Samu Kerevi hobble around with a knee injury.
"It's obviously really disappointing for James to suffer such a serious injury this early in the season," said Reds coach Nick Stiles.
"We'll miss his contributions on the field but, knowing the sort of bloke he is, he'll still be heavily involved from the sidelines.
"We're fortunate that we've got Stephen Moore in the side, who is the current Wallabies skipper. He will take over the captaincy in Slipper's absence."
After losing Slipper in the first half, then having winger Eto Nabuli shown a yellow card for cynical play in the 45th minute, the Reds were in total disarray - down to 13 men - when Cooper received his straight red.
Reds winger Izaia Perese escaped sanction for a possible tip tackle in the same passage of play, quite likely saved by Cooper's more serious infringement.
Leading 15-0 at the interval, the Lions piled on further tries to hooker Malcolm Marx and a second-half treble to winger Courtnall Skosan - the second a brilliant individual effort - to underline the 2016 finalists' comprehensive bonus-point win.
Duncan Paia'aua scored for the Reds in the 69th minute after a clever offload from fullback Karmichael Hunt, and replacement prop Taniela Tupou also bagged a consolation five-pointer in the final minutes from close range.
"We were pretty much humbled tonight," Slipper said.
"Credit has to go to the Lions; they're a physical team who can score points.
"Our discipline has to be one of (the lessons to take from the game). When you have a couple of cards, and then our set piece wasn't really functioning, it's hard to win games under that sort of pressure.
"I said before the game that if we play our game and play it well, we'll be competitive, and we didn't do that at all."
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