"These sanctions are barbaric. This is a war against a nation...But the Iranian nation will defeat them," Khamenei said in a speech during a visit to the northeastern province of North Khorasan, broadcast on state television.
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He also accused the West of "lying" over its offer to lift sanctions in return for Iran furnishing guarantees to back its claims its atomic program is intended for civilian purposes only.
The West suspects Iran is seeking a nuclear weapons capacity, despite repeated denials from Tehran.
Khamenei said the sanctions had created "problems" for the country, and that "some mismanagement" of the draconian measures was adding to those problems. He did not elaborate.
The supreme leader also rejected the notion that sanctions were linked to Iran's nuclear efforts, as the West claims they are.
"The enemies - the US and some European governments - are nowadays linking the sanctions to (Iran's pursuit) of nuclear energy. They are lying," he said.
He argued that his country has been targeted by sanctions since the 1979 Islamic revolution for its "independence and resistance" against world powers.
Western power have tightened an economic sanctions regime against the Islamic republic over the past two years, causing a drop in Iran's oil exports and production, a collapse of its currency, slowing its economy and boosting the ranks of the jobless.
Talks between Iran and major powers on the nuclear impasse have stalled for years. Tehran is also under several sets of international sanctions imposed by the UN Security Council.
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