"There is no linkage whatsoever of the nuclear discussions with any other issue," Kerry told reporters in Beijing, where he was attending annual Asia-Pacific Economic Cooperation (APEC) forum meetings.
"And I want to make that absolutely clear. No conversation, no agreement, no exchange, nothing has created any kind of a deal or agreement with respect to any of the events that are at stake in the Middle East."
The top US diplomat added a slight qualification by saying that he was not aware of any such discussions, but quickly expressed confidence that he would be in any loop.
"I'm confident I am aware of what the president has been doing and saying with respect to this issue," he said.
Kerry spoke after the Wall Street Journal reported Thursday that US President Barack Obama has secretly written to the supreme leader of Iran, which is overwhelmingly Shiite, to discuss possible cooperation against Sunni Islamic militants provided there is a nuclear deal.
Obama sent the letter last month to Ayatollah Ali Khamenei describing what he called a "shared fight" against the militant Islamic State group, the paper said, citing "people briefed on the correspondence".
"No one to my knowledge has confirmed or denied whether or not there is a letter, or was a letter, and I'm not going to comment on what a president of the United States and the leader of another country may or may not communicate privately," Kerry said before issuing his denial of any linkages.
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Kerry's comments on the letter follow those by White House spokesman Josh Earnest, who also declined "to discuss private correspondence between the president and any world leader".
Iran, the US and other countries including Russia are negotiating a complex deal to rein in Tehran's nuclear ambitions in exchange for an easing of crippling international sanctions against the Islamic Republic.
Kerry will Sunday meet with Iranian Foreign Minister Mohammad Javad Zarif as well as EU foreign policy chief Cathy Ashton in Oman for a fresh round of nuclear talks.
They will meet in Muscat, which hosted secret Iran-US talks in 2012, widely credited for bringing Tehran back to the nuclear negotiations.
After the Muscat talks, the negotiations will move to Vienna on November 18 for a final push with all the P5+1 partners towards a November 24 deadline.
The P5+1 includes the United States, France, Britain, Russia and China, plus Germany.
Kerry, who met Russian foreign minister Sergei Lavrov on Saturday in Beijing, praised Moscow's role in the nuclear talks, saying it "has been a constructive, engaged, serious partner" on the issue.