"Imposing useless sanctions on Iran's Supreme Leader (Ayatollah Ali Khamenei and the commander of Iran's diplomacy (Foreign Minister Mohammad Javad Zarif) is the permanent closure of the path of diplomacy," Foreign Ministry spokesman Abbas Mousavi said in a tweet.
"Trump's desperate administration is destroying the established international mechanisms for maintaining world peace and security."
US President Donald Trump targeted Khamenei and other top Iranian officials with sanctions on Monday, taking an unprecedented step to increase pressure on Iran after Tehran's downing of an unmanned American drone.
Washington said it will also impose sanctions on Iran's Foreign Minister Zarif this week.
Khamenei is Iran's utmost authority who has the last say on all state matters.