The contests will provide the first test of whether the Republican establishment's desperate effort to end the inevitability of his drive to the party's nomination is having any effect among voters.
The brash billionaire is ahead in the all-important delegate count for the Republicans, having won 10 of the 15 states that have voted to date in the process that determines the nominees for both parties.
Hillary Clinton is well ahead of rival Senator Bernie Sanders on the Democratic side, hoping to expand her lead as she inches closer to securing the nomination.
The former secretary of state is expected to dominate in Louisiana, the weekend's biggest prize, because of its large African-American vote.
But Sanders could bounce back in the other two states - plus Maine, which holds its Democratic caucus today - because they have largely white populations, a demographic with which Sanders has done well.
The GOP race has been winnowed down to four candidates - the political outsider Trump, Florida's Rubio, Senator Ted Cruz of Texas and Ohio Governor John Kasich - with many in the Republican establishment in virtual panic over whether anyone can stop Trump's march to the nomination.
Trump made waves when he cancelled a scheduled yesterday morning appearance at the Conservative Political Action Conference near Washington, opting instead to hold a rally in Wichita, Kansas.
The move angered members of the American Conservative Union which hosts CPAC.
"I think it was a big mistake for Donald Trump not to be here," ACU chairman Matt Schlapp told CNN.
"It's the establishment. The establishment is against us," Trump said.
"We're going to change things so badly and so quickly, it's going to go so fast, and you're going to be so proud.
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