In a new travel warning, the State Department said Russia may refuse to acknowledge US-Russian dual citizenship.
The warning added that US citizens had already "been interrogated without cause and threatened".
Russian officials have downplayed the updated travel advisory.
It is unclear how many US citizens are travelling or living in Russia and a State Department spokesperson told the BBC that it does not track the travel of US citizens abroad.
Following the Russian invasion of Ukraine in February 2022, several thousand Americans reportedly fled the country.
In its newly updated travel warning, the State Department said those still in Russia face the potential for "harassment and singling out".
Dual citizens also face the prospect of being conscripted as part of a wider Russia military mobilisation to support operations in Ukraine, it said.
"Russia may refuse to acknowledge dual nationals' US citizenship, deny their access to US consular assistance, subject them to mobilisation, prevent their departure from Russia, and/or conscript them," the warning reads.
A number of US citizens - including former and current government personnel and private business people - have already been taken into custody, interrogated and harassed, according to the State Department.
"Russian security services may fail to notify the US Embassy of the detention of a US citizen and unreasonably delay US consular assistance," the warning reads. "Russian security services are increasing the arbitrary enforcement of local laws to target foreign and international organisations they consider 'undesirable'."
In a statement quoted by Russian news agency TASS, Kremlin spokesperson Dmitry Peskov said that the US had issued similar warnings "many times".
"This is not the first time we have heard this," he said.
The last US warning for its citizens to leave came in September, when Russian authorities announced a partial mobilisation of military reservists.
Mr Peskov also said that any dual US-Russian citizens "are primarily Russian citizens, regardless of what citizenship they have".
Besides Russia, the State Department has "do not travel" advisories for 18 other countries including Afghanistan, Syria, Haiti, North Korea, Somalia, Ukraine and Yemen.
Watch: One Russian's exhausting ordeal to escape conscription