Marler is set to be replaced in the match-day squad by Alex Corbisiero, who has made two starts for London Irish over the last fortnight after recovering from a knee injury of his own.
Lancaster said: "Joe Marler has a grade one MCL so it is likely he won't be available for Saturday. He'd be out of the equation I think. Alex Corbisiero would come back into the equation for him."
The potential change at loose-head prop is one of a number Lancaster is considering as England aim to bounce back from their 20-14 defeat to Australia.
Tom Wood appears a likely starter at blindside flanker while London Irish centre Jonathan Joseph has also come back into the equation after shaking an ankle injury.
"The selection for South Africa will be based on a variety of things," said Lancaster First and foremost the challenge of South Africa, their physicality and the performances they have been putting in on this tour."
Geoff Parling, Tom Palmer, Manu Tuilagi, Charlie Sharples and Tom Youngs all sat out training on Monday with "bumps and bruises as opposed to anything too serious" from the weekend.
England held a review session in the morning, in which the key decisions not to kick penalties for goal were analysed and the focus shifted to the Springboks.
"We have to take what we can out of the game," Lancaster said. "We talked about all the decisions made in the game. I will support the players in their decision because it is a real-time decision.
"But we have to make sure we get those decisions correct. Did we get them all right? There are some that have been reviewed but I won't criticise the players for having a mindset to win the game. There were plenty of opportunities to win it. We were in the game with less than five minutes to go but the reality is we didn't win it."