Props Cian Healy (ankle ligaments) and Gethin Jenkins (calf muscle) were already flying home on Sunday, but the Lions are now set to lose star Ireland wing Tommy Bowe. Ulster try-machine Bowe, a strong bet to have been in the Lions' first Test team against Australia on June 22, suffered a suspected broken hand during the 22-12 victory over Queensland Reds.
Bowe's Ireland and Lions team-mate O'Connell said: "They (Lions) move on fairly quickly, they start planning what they've got to do to get it right, and the squad kind of has to move on as well. You are disappointed for them, but the squad has to move on."
Bowe returned to action in time for the Lions squad announcement just over two months ago after missing a large chunk of the season through injury, playing in Ulster's Heineken Cup quarter-final defeat against Saracens at Twickenham.
If, as expected, Lions head coach Warren Gatland summons a replacement, then players like Ireland's Simon Zebo, young Englishman Christian Wade and Scotland's Tim Visser could all be in the frame.
"It doesn't look good, and after him working so hard to get back from an injury he's fairly disappointed," O'Connell added. "It doesn't look good at the moment. It's hard to fully say, but I don't think they are too confident at this stage. Unfortunately, it's another Irish guy down.
"The guys that get injured, they are very disappointed, obviously, but you've just got to get on with it.
"It's disappointing for the guys, especially a guy of Tommy's experience. Certainly in the backs, while we have experience we have a lot of young guys as well, and it was good to have a winger of his kind of experience there.
"You have got to be positive about it, and they had spoken early on (saying) that this was going to happen - guys were going to be brought over, guys were going to get plenty of chances, so you've just got to deal with it and get on with it."
O'Connell went on as a second-half substitute and played an integral part in keeping a fired-up Reds side at bay. Although they outscored the Lions two to one on tries, Owen Farrell's 17-point haul made the difference.