Nikki Haley and Ron DeSantis will be alone on the debate stage for the first time as they wage an increasingly contentious push to become the primary Republican alternative to Donald Trump.
With other contenders absent, the stakes are high for both Ms Haley, the former UN ambassador, and Mr DeSantis, the Florida governor.
They hope that a strong debate performance in Iowa will lift their campaigns in the final days before Monday’s caucuses, where a strong showing could provide much-needed momentum as the campaign for the Republican presidential nomination intensifies.
Wednesday’s moment is especially important for Ms Haley, a politician long known for her disciplined approach to messaging.
That reputation has been tested recently after a series of gaffes, including her failure to mention slavery as the root cause of the Civil War and a quip that New Hampshire voters will have a chance to “correct” the results that emerge from Iowa.
For all the attention on Ms Haley and Mr DeSantis, the commanding frontrunner in the race will again be absent.
Mr Trump, who is aiming to quickly close in on securing his third consecutive Republican nomination, will skip the debate hosted by CNN and instead appear on Fox News.
The debate will still offer Ms Haley a chance to reset a campaign that has come under fresh scrutiny by everyone from her Republican rivals to President Joe Biden, a sign that her rivals in both parties see her as a rising contender.
While she is likely to pay more attention to Mr Trump as her allies argue she is the only person equipped to beat him, Mr DeSantis is expected to train his focus on Haley.
“Now she’s in a situation where she’s getting scrutiny, and it’s almost like every day she answers questions, something happens where she’s putting her foot in her mouth,” Mr DeSantis told reporters after appearing on a Fox News town hall.
After several debates filled with candidates who likely have minimal chances to win the nomination, many expected caucusgoers said they planned to pay close attention to a debate featuring Mr Trump’s main opponents.
Terry Snyder of Waukee, outside Des Moines, said she caucused for Mr Trump in 2016 but that he had “too much baggage” this time.
She wants to have a clearer picture without the crosstalk of a bigger stage.
“I get aggravated because they talk over each other, so you don’t learn anything,” Ms Snyder said.
“So hopefully with just two people it’s not going to be like that.”
Some of Ms Haley’s strongest moments have come during the previous four debates, as she has sparred with all her on-stage rivals.
A CNN/UNH poll conducted in New Hampshire this week suggested that Ms Haley could be approaching Mr Trump’s top spot in the state.
About four in 10 likely Republican primary voters in New Hampshire chose Mr Trump, while about one-third picked Ms Haley.
While for months she has taken questions at many of her campaign events, styled as town halls during which she entertains Q&A from the gathered crowd, Ms Haley has rarely spoken after events with the reporters covering her events, held news conferences or sat for print interviews.
She did not speak to reporters after her own Fox News town hall on Monday, a day before Mr DeSantis’ appearance.
