The West "keeps saying pressure against Iran is aimed at forcing the Islamic Republic to return to the negotiating table" about its nuclear program, Ayatollah Ali Khamenei said in remarks carried on state television.
"But when did we leave the table that now we need to return?" he asked during his visit to the northeastern province of North Khorasan.
"Their real objective is [forcing] the Iranian nation to surrender to their bullying at the negotiating table...[but] you are too weak to bring Iran to its knees," Khamenei said.
His remarks came a day after the European Union toughened sanctions against Tehran, targeting its dealings with Iran's banks, shipping and gas imports and banning trade in metals.
Without directly mentioning the sanctions, Khamenei accused the European leaders of seeking to bully Iran.
"European officials are still stuck in the bullying mindset of the colonial 19th century, but they will face many problems in the face of the resistance of the Iranian nation and officials," he said.
Khamenei has called the Western sanctions "barbaric"  and said they amount to "a war against a nation ." But he has said Iran can overcome problems caused by the sanctions.
Foreign Ministry spokesman Ramin Mehmanparast also denounced the sanctions on Tuesday , describing them as "illegal, unwise and inhumane," while vowing not to retreat on the country's nuclear program.
The West is involved in talks with Tehran on the nuclear impasse, but those negotiations have stalled for years. Efforts to restart them this year failed, despite three rounds of face-to-face talks between representatives of Iran and the five permanent members of the Security Council, plus Germany.
Western powers suspect Iran is using to the program to develop its atomic weapons capacity. Tehran and and its main backer, Russia, insist the program is being developed solely for peaceful purposes.
Israel and the United States have both refused to rule out the possibility of an armed strike on Iran's nuclear facilities.
Five Iranian nuclear scientists have been assassinated since 2010. Destructive cyber-attacks have also been launched against Iran’s atomic research program. 
Iran has accused Israel of being behind the killings and sabotage.