Vladimir Kara-Murza has suffered "multiple organ failure," is on dialysis and is being artificially ventilated, his lawyer, Vadim Prokhorov, wrote on Facebook.
Kara-Murza, 35, is "currently in a stable but critical condition" in a hospital, Prokhorov said by phone. "It is a very, very difficult situation," he added.
Prokhorov said he doesn't believe this illness is related to Kara-Murza's previous health problems, but said he suspects it is another case of poisoning.
"None of the medical staff can explain the reason for his current condition. Both last time and once again now," he said.
He said he has no direct proof his client was poisoned.
US Sen. Marco Rubio, R-Florida, said Putin should be held accountable if there is evidence the government poisoned Kara-Murza.
"Vladimir Putin does not deserve any benefit of the doubt here, given how commonplace political assassinations and poisonings have become under his regime," said Rubio, a frequent Putin critic. "I am praying that Kara-Murza's condition improves."
He urged the White House and the State Department to question Russian authorities about the case.
Kara-Murza is part of the Open Russia foundation, an organization of anti-Putin activists who call for open elections, a free press and civil rights reforms.
Moscow denies involvement in 2015 health scare
CNN spoke to Kara-Murza in 2015, months after a mysterious illness nearly killed him.
"I fell into a coma, all of my major organs began failing, one after another. It was the kidneys first, then the lungs, the heart, the liver," he said at the time.
He said he believed his 2015 suspected poisoning was a politically motivated attack.
"Frankly there is no other possible reason," he said. "I don't have any money dealings. I don't have any personal enemies. I didn't steal anybody's wife."
The case had parallels with the killing of former Russian agent Alexander Litvinenko
A British public inquiry into that 2006 poisoning found two former Russian agents responsible for carrying out the poisoning with the radioactive isotope Polonium-210. Its final report concluded that Putin was "probably" aware of the operation.
The Russian Foreign Ministry dismissed the UK inquiry as politically motivated and the Kremlin said Russia wasn't involved.
In February 2015, a leading Russian opposition figure and friend of Kara-Murza, Boris Nemtsov, was shot to death on a bridge near the Kremlin as he walked home from a restaurant. Kara-Murza became ill four months later.