(CNN) -- Rick Santorum has a very good chance of scoring a major victory in Saturday's Republican presidential primary in Louisiana, but the big question is whether it will still matter.
Polls released the past couple of days indicate the former senator from Pennsylvania with a double-digit lead over former Massachusetts Gov. Mitt Romney and former House Speaker Newt Gingrich, among those likely to vote in Louisiana's contest.
But since Romney's 12-point victory over Santorum, his nearest rival in the battle for the GOP nomination, in the Illinois primary on Tuesday, the conversation appears to have changed.
"Santorum can't lose this and it doesn't look like he will. He will argue that the victory proves Romney can't win in the South, the bedrock of the Republican Party. But will anyone be listening," CNN Chief Political Correspondent Candy Crowley said. "Inside the party, there is a full-blown push to close this thing down," evidenced by the support for Romney from Jeb Bush and Jim DeMint.
Jeb Bush, the brother of former President George W. Bush and the popular and influential former Florida governor, endorsed Romney after his victory in Illinois, and urged that it was time to close ranks around Romney. DeMint, the conservative senator from South Carolina and kingmaker among tea party supporters, all but officially backed Romney Thursday.
A week-and-a-half ago, Santorum narrowly edged out Gingrich and Romney to capture primaries in Alabama and Mississippi. But he lost in a landslide to Romney last weekend in Puerto Rico, and then fell again in Illinois.
"Santorum can't just win, he has to win big. He's the one who needs to 'shake up' this race. Another ho-hum win in the South doesn't cut it. He's on a political bridge to nowhere and is running out of time to change destinations," said Bruce Haynes, a GOP strategist and managing partner of Purple Strategies, a bipartisan public affairs consulting firm.
According to a CNN estimate, Romney has 563 delegates, more than twice the 251 Santorum has in hand, and nearly halfway to the 1,144 delegates needed to clinch the nomination.
Twenty delegates are up for grabs Saturday in Louisiana's primary, which is closed, meaning only registered Republicans can vote in the contest.
Santorum has spent much of this week campaigning in Louisiana. Speaking to voters Friday in West Monroe, he said that the state has an opportunity "to do what's been done five, or eight or 10 times in this race, and that is to change the dynamic in this race."
One question: How much, if at all, will a controversial comment from Santorum on Thursday suggesting that if Romney were the nominee, it might be better for voters to stick with President Barack Obama in November?
"You win by giving people the choice. You win by giving people the opportunity to see a different vision for our country, not someone who is just going to be a little different than the person in there," Santorum said in a speech in San Antonio, Texas. "If we are going to be a little different, we may as well stay with what we have instead of taking a risk in what may be the Etch A Sketch candidate for the future."
Friday, Santorum clarified, saying, "I have said repeatedly I will vote for whoever the Republican nominee is and I will work for them. Barack Obama is a disaster but we can't have someone who agrees with him on some of the biggest issues of the day and that is the problem with Gov. Romney. He doesn't provide the clear choice we need."
Gingrich, who came in last in Illinois after being edged out by Rep. Ron Paul of Texas for third place, has campaigned nonstop in Louisiana since Tuesday. At an event Friday in in Port Fourchon, he pointed to gaffes by both of his major rivals over the past few days.
"We don't know what is going to happen tomorrow yet. I think Sen. Santorum's mistake last night is likely to prove expensive. I think the Etch A Sketch comment by Gov. Romney's communications director is probably not helping him. We have won two straw polls among tea parties by huge margins in the state in the last week and I am cheerful about going forward," said Gingrich, referring to a recent incident in which a Romney adviser likened to redrawing Romney's political profile to using an Etch A Sketch.
Gingrich won South Carolina's primary in January and carried his former home state of Georgia earlier this month, but lost in neighboring Tennessee and Alabama, and Mississippi. If he loses again in Louisiana, will the chorus of calls for him to end his bid for the nomination grow louder?
"Newt Gingrich is going to get out, or not, on his own schedule, and in keeping with his own pocketbook. It's probably time to stop calling every race 'do or die' for Gingrich, since recently he has been 'not doing' and carrying on," said Crowley, anchor of CNN's "State of the Union."
"Gingrich's campaign is a conversation in search of an audience. Voices from all quarters of the GOP are growing hoarse from calling on Gingrich to drop out. It's clear he's not listening, and he'll drop out when it suits his own purposes, whatever they are," said GOP strategist Haynes.
Of the top three candidates, Romney, the overwhelming front-runner, has the least at stake. He has yet to win in the Deep South and isn't expected to reverse the trend in Louisiana. Friday was the only day this week he spent campaigning in the state.
"You've got a lot of delegates here. I want, well I'd like all of them. I'm probably not going to get all of them but I want to get as many as I can. So I want to ask you to get out there and vote and give me a good send-off," Romney told voters in the New Orleans suburb of Metairie.
Ron Paul, in the single digits in the polls in Louisiana, only briefly campaigned in the state and isn't expected to impact Saturday's results.
After Louisiana, the primary calendar picks up again on April 3 with contests in Wisconsin, Maryland and the District of Columbia.