"The outbreak of a conflict will be a big, big, big problem for all of us, and I worry a great deal about the unintended consequences of a strike," Admiral Mullen said.
Apart from saying that "it's pretty hard to be specific about" the issue, the top-ranking US military official did not expand on his comments.
Mullen, who was speaking to journalists during a visit to Israel, went on to say however that US President Barack Obama had been "very clear that from a policy standpoint, Iran cannot have a nuclear weapons."
"We haven't taken off any option from the table," the admiral said, using diplomatic language for keeping open the possibility of launching military strikes.
Mullen is due to hold talks with Israeli Defence Minister Ehud Barak along with other military officials during his visit to the Jewish state, as part of a tour of the Middle East.
US Secretary of State Hillary Clinton was also in the region on Sunday trying to drum up support in the Gulf for imposing tougher sanctions against Iran over its nuclear programme.
Tehrann, which rejects accusations of seeking to build a nuclear bomb, said on Tuesday it has started the process of producing 20 percent enriched uranium, defying Western threats of fresh sanctions.
