The Northampton Saints second-row has been sidelined due to a shin injury and joins back-row duo Tom Wood and Tom Croft on the casualty list.
"He's gutted," Saints director of rugby Jim Mallinder told BBC Sport.
"You want to be involved in the big games. But he'll probably not play for Saints or for England."
It is the latest injury problem to hit Lawes, who missed the first two matches of the Six Nations before suffering another set-back upon his comeback against Wales
Lawes was ruled out the first two matches of the Six Nations and was back in the treatment room after an appearance against Wales.
"He's been a bit unfortunate [but] he'll come back fighting fit. He's got a lot of years to go," added Mallinder.
"We were hoping that he might play some part this season, but it looks like he's not recovered enough from his shin injury.
Lawes, who has been capped 14 times by England, is a candidate for next year's Lions tour to Australia.