Lyon hurt his right calf while fielding in the final session on day two, before leaving the ground on crutches and having scans overnight.
Those scans have since confirmed a significant strain, with Australia officials to determine the length of his time out at the end of the Lord's Test.
It is believed Lyon may bat on the final days in London if required but after arriving at the ground on crutches again on Friday any involvement beyond that is unlikely.
ICC rules dictate that if Lyon was to bat, he would not be able to use a runner.
"Nathan Lyon has been diagnosed with a significant calf strain," a Cricket Australia spokesman said.
"He will require a period of rehabilitation after this match is concluded.
"A decision regarding his availability for the remainder of the series will be made at the conclusion of the game."
Australia have a three-day turnaround between the end of the Lord's Test and Thursday's third match at Headingley.
The fourth and fifth Tests at Old Trafford and The Oval respectively are also scheduled for July, meaning anything beyond a four-week recovery would rule Lyon out of the series.
As the sole back-up spinner on tour, and after impressing in India earlier this year, Todd Murphy is the man likely to replace Lyon.
Mitchell Swepson is in England playing county cricket, while Matthew Kuhnermann has recovered from a back injury and would be fit if called upon.
But at this stage, Australia have made no plans to call a replacement player into the squad.
Murphy has 12 first-class games to his name but has not played since Victoria figured in the Sheffield Shield final in March.
Any injury-enforced absence will also end Lyon's run of 100 straight Test matches, as well as hopes of reaching the 500-wicket mark at Lord's with his tally standing at 496.
Speaking before his milestone Test earlier this week, Lyon backed the rising depth of Australia's spinners and said he was on hand to help them.
"If I could do anything to help the younger spinners ... my phone is always going to be on for them," Lyon said.
"When came into Australia and Test team I definitely didn't have anyone that I could really lean on and ask my questions and ask for support.
"But I'm really hoping that for Todd and these guys, I can help them.
"They're willing to listen and they're willing to ask questions.
"We're having some really good discussions in our spinners meeting about different things, different methods, different shapes and everything."
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