With Donald Trump up by more than 40 percentage points in most opinion polls and Iowans set to choose their preferred nominee on Jan. 15, DeSantis and Haley are in a rush to establish themselves as the obvious alternative for voters looking to move beyond the former president.
Former tech entrepreneur Vivek Ramaswamy and former New Jersey Governor Chris Christie will also take the debate stage in Tuscaloosa, Alabama - but the spotlight will be on DeSantis and Haley.
DeSantis holds a small advantage over Haley in national polls. But Haley has been closing the gap, and has a substantial edge over DeSantis in New Hampshire and her home state of South Carolina - crucial states in the nomination battle because they're among the first to pick a nominee.
The two are effectively tied in Iowa, where the first Republican contest will be held on Jan. 15.
With no additional debates currently scheduled, Wednesday's televised clash could be the last chance for Haley or DeSantis to land a lasting blow against their opponent in front of a national audience.
"The two people on the stage that have a shot at challenging Trump one-on-one are DeSantis and Haley," said David Kochel, a longtime Republican strategist in Iowa.
Kochel said it was far from guaranteed either candidate would turn in the kind of performance needed to reshape the race. Trump himself is skipping the debate and will be hosting a fundraiser in Florida, meaning no candidate will have an opportunity to spar with the frontrunner.
Ramaswamy, who is in distant fourth place, will also be on stage. He is likely to go after Haley and DeSantis aggressively in a bid to jump-start his campaign, which could derail the DeSantis-Haley showdown.
Haley received plaudits from voters and donors for the way in which she handled a heated exchange over foreign policy with Ramaswamy during the first debate in August. But more recent exchanges between them have been more of a wash for both candidates, and have devolved into more personal attacks.
During the third debate in November, Haley called Ramaswamy "scum" after he said Haley's daughter had used TikTok, the short video app owned by a Chinese company, which many Republicans view as a national security risk.
Former Governor Christie barely met the minimum polling thresholds set by the Republican National Committee to qualify for the debate. The former federal prosecutor once supported Trump, but has become one of his most vocal opponents and will be sure to attack the former president on stage.
The debate will take place at the University of Alabama at 7 p.m. CST (0100 GMT). It will be hosted by subscription-based television network NewsNation, conservative political journal the Washington Free Beacon, The Megyn Kelly Show on Sirius XM satellite radio and the Rumble video platform.
(Reporting by Gram Slattery; editing by Ross Colvin and Jonathan Oatis)
By Gram Slattery
