It would be an unprecedented slight, but it might not matter.
Pompeo's nomination faces significant opposition on the Senate Foreign Relations Committee, where Republicans hold an 11-10 majority over Democrats. They voice concern that Pompeo would act as a hawkish advocate for military force, not diplomacy, and would fail to serve as a counter-balance to Trump.
Mr. Pompeo now heads the Central Intelligence Agency but was nominated by President Trump to take over at the State Department after former Secretary Rex W. Tillerson was sacked.
"I don't create this decision lightly or without reservations", Coons said in a statement Friday. Both, however, found reasons to support Pompeo's confirmation, owing to his qualifications and the need for the State Department to have capable leadership.
Yet Mr Tillerson was confirmed on a party-line vote of 56-43.
Even if Monday's vote is negative, his nomination will still go to the full Senate.
Trump has tweeted several favorable comments about Pompeo, whom he recently dispatched to Pyongyang to meet with North Korean ruler Kim Jong Un in advance of Trump's planned summit with Kim over denuclearization of the Korean peninsula.
"Nothing could better underscore the importance of getting America's top diplomat in place for such a time as this", White House spokeswoman Sarah Huckabee Sanders tweeted. "I personally know Mike Pompeo". Rand Paul have announced they oppose making Pompeo the country's top diplomat.
"Pompeo is a proven national security leader", one such ad says. Heidi Heitkamp as Democrats who have to publicly announced their support for Pompeo. Bob Corker, blames partisan politics for opposition to Pompeo, saying the Central Intelligence Agency chief is just as qualified as past nominees for secretary of state.
In the Senate Foreign Relations Committee, however, the numbers on the panel are against him.
Failing to win the panel's vote of approval "is not a lethal wound, but it's one that leaves a scar", he said.
Sen. Chris Coons, D-Del., who was on the list of past Democrats around the panel to announce that his vote, " said he is concerned that Pompeo "will embolden, " as opposed to reasonable or control" Trump's "most populous and instincts that are unsafe".
"I realize my Democratic friends in many cases feel like that in supporting Pompeo, it's a proxy for support of the Trump administration policies, which many of them abhor".
The editorial boards of the New York Daily News and USA Today endorsed Mike Pompeo's confirmation as secretary of state just as senators gear up to vote on the president's nominee.
She said Mr Pompeo convinced her that he's committed to empowering the diplomatic corps and filling key vacancies such as the United States ambassador to South Korea. This would still allow a vote in the full Senate.