O'Driscoll, taken out of the game inside two minutes by a double spear-tackle from Mealamu and All Blacks skipper Tana Umaga, could struggle to play again before Christmas after dislocating his shoulder and may require surgery.
Hill, meanwhile, has suffered a career-threatening knee injury, rupturing his anterior cruciate ligament only two months after returning to the game following another major knee problem.
"We are hugely disappointed, no-one more than me with what happened on Saturday. It was a particularly disappointing performance and we let a lot of people down, especially ourselves," said head coach Woodward.
"It wasn't a good night, but we have still got to front-up big time. I believe we can beat New Zealand at the weekend.
"I went through everything in detail. Every time England had a particularly bad performance, it always came back to one or two things, either the scrum or the lineout.
"You just can't play at this level, unless you can guarantee your own ball 95 per cent of the time. Things went on in the lineout that were very disappointing from our point of view, and I think that is where the game just drifted away."
Woodward also conceded he may have got one or two selections wrong and will have to make changes for the Second Test at the Westpac Stadium for a game he must win.
"There will obviously be a few changes based on injuries. I wasn't expecting to pick up this amount of injuries if I am brutally honest, and we have just got to readjust our plans slightly," he added.
"Going into the game, I was obviously 100 per cent convinced that I got selection right but with hindsight, I may have made a couple of errors and I intend to fix those come the weekend.
"We've got six or seven players who we don't think will be available for selection on Tuesday (against Manawatu), based on injuries, so we are having to give the medical team another 24 hours to provide a full report.
"Undoubtedly, there will be players playing or benching on Tuesday who will be playing or benching in the Test match on Saturday."
Tries in each half from All Blacks lock Ali Williams and wing Sitiveni Sivivatu sealed victory for the home side but it was at the lineout that the Lions really struggled.
They lost eight on their own ball, while Williams' try came after he caught hooker Shane Byrne's throw and galloped over from 15 metres.
Forwards coach Andy Robinson promised an improvement in that area ahead of Saturday's crunch encounter.
"We were completely outplayed in the lineouts. At times, we got our communication wrong, and we will deal with it this week," he said.