"The enemies have united and are using all their means, money, weapons, policies and security services to create problems for the Islamic regime," Ayatollah Ali Khamenei said in a speech carried on state television.
Iranian officials have said online accounts in the United States, Britain and Saudi Arabia are fomenting protests.
A fifth night of unrest saw six protesters killed during an attack on a police station in Qahderijan in the central province of Isfahan, state TV said today.
The estimated death toll is now 21 since protests began in second city Mashhad and quickly spread to become the biggest challenge to the Islamic regime since mass demonstrations in 2009.
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"The enemy is always looking for an opportunity and any crevice to infiltrate and strike the Iranian nation," Khamenei said.
The unrest appears leaderless and focused on provincial towns and cities, with only small and sporadic protests in Tehran last evening where a heavy police presence was reported.
A Revolutionary Guards spokesman said they had not been requested to intervene directly, but they requested the public to report "seditionist elements".
"We will not permit insecurity to continue in any way in Tehran. If it continues, officials will take decisions to finish it," said Esmail Kowsari, a deputy commander for a local branch of the Guards, on state television.
Ali Shamkhani, secretary of the Supreme National Security Council, described the unrest as a "proxy war against the Iranian people".
President Hassan Rouhani has tried to play down the unrest, which began over economic grievances Thursday but quickly turned against the regime as a whole with chants of "Death to the dictator".
"This is nothing," he said in a statement on the presidency website on Monday, vowing the nation would deal with "this minority who... insult the sanctities and values of the revolution".
Pro-regime rallies were held across several towns and cities -- reflecting continued support among a large conservative section of society.
Rouhani came to power in 2013 promising to mend the economy and ease social tensions, but high living costs and a 12 percent unemployment rate have left many feeling that progress is too slow.
The young are most affected, with as many as 40 percent out of work according to analysts, and rural areas particularly hard-hit.
"The situation is far worse in provinces. Agriculture has been destroyed. I know many who have left the north of the country to come to Tehran to work," she added.
Rouhani acknowledged there was "no problem bigger than unemployment" in a speech on Sunday, and also vowed a more balanced media and more transparency.
US President Donald Trump, who has repeatedly criticised Tehran over four days of demonstrations, said it was "time for a change" and that Iran's people were "hungry" for freedom.
"We believe that there should be meaningful debate about the legitimate and important issues the protesters are raising and we look to the Iranian authorities to permit this," Johnson said in a statement.
Turkey today expressed concerned about the protests in a statement that called for "common sense" to "prevail to prevent any escalation".
In 2009, authorities ruthlessly put down protests against the re-election of hardliner Mahmoud Ahmadinejad. At least 36 people were killed in 2009, according to an official toll, while the opposition says 72 died.