Mr Mattis called Iran the “single biggest destabilising element” in the Middle East during a rare press conference at the Pentagon along with Chairman of the Joint Chiefs of Staff General Joseph Dunford.
He warned they are “going to be held to account for it” but did not going into detail about what that entailed.
The Marine general did acknowledge he felt there was “less willingness to be confrontational” on Iran’s part, but added they are still “fundamentally” a destabilising factor in the region.
Mr Mattis also clarified: “Our problem is not with Iran, it’s with the Iranian regime leadership, not the Iranian people. I just want to separate those two as well.”
Iranian President Hassan Rouhani, addressing the country's economic woes exacerbated by US sanctions, said Tehran will defeat any "anti-Iranian" officials within the White House as it recovers from virtual economic isolation.
One of the sticking points for Mr Mattis and the Trump administration is Iran’s involvement in the Syrian conflict, during which millions have died or fled the country under Mr Assad’s regime.
Mr Mattis asked emphatically, “what are they doing in Syria in the first place?”
He claimed Iran was “propping up” Mr Assad, who has “committed mayhem and murder on his own people”.
Answering his own question, the defence secretary said Iran “has no business” being in the middle of the “civil war”.
He added that the Trump administration is working with Russia, who may have the “traction” and “persuasiveness” to ask Iran to leave, but did not address the issue of Mr Assad asking Tehran to be involved in the first place.
On Syria, Mr Mattis noted the administration’s goal is to move the country “into the Geneva process” in order to establish a government not led by Mr Assad.
Mr Assad “has denied them [a future] with overt Russian and Iranian support”.
Experts have said the US-Iran relationship has eroded under Mr Trump due to not re-certifying the Iran nuclear deal in May 2018.
Despite the evidence provided by the United Nations on Tehran’s compliance with the deal, Mr Trump said it was too lenient on Iran and has maintained the idea that the country has violated portions of it.
Not re-certifying the 2015 deal and abandoning it meant opening the door for harsher economic sanctions to be placed on the country, the mitigation of which was a key inducement for Iran to comply with the historic deal which sought to stymie the development of its nuclear weapons development programme.
“There are few issues more important to the security of the US than the potential spread of nuclear weapons, or the potential for even more destructive war in the Middle East. That’s why the US negotiated the Joint Comprehensive Plan of Action (JCPOA) in the first place,” the former president had written.
He added: “At a time when we are all rooting for diplomacy with North Korea to succeed, walking away from the JCPOA risks losing a deal that accomplishes – with Iran – the very outcome that we are pursuing with the North Koreans.”
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