Rep. Bill Cassidy (R-La.) will challenge Sen. Mary LandrieuMary Loretta LandrieuSenate GOP rejects Trump’s call to go big on gun legislation Project Veritas at risk of losing fundraising license in New York, AG warns You want to recall John McCain? Good luck, it will be impossible MORE (D-La.) in 2014, a source close to his campaign confirmed to The Hill.

He'll announce his bid on Wednesday in a video message.

Cassidy has been preparing for a run behind the scenes for the past few months, and announced on Monday that he raised more than $500,000 in the first quarter of this year, a strong haul for a Senate candidate this early in the cycle. He's been traveling to events outside his district and recently signed up prominent Louisiana consultants Jason Herbert and Scott Hobbs to help.

He is the first Republican to announce his intention to run for the seat, but a handful of other potential GOP candidates, including Rep. John FlemingJohn Calvin FlemingCoast Guard suspends search for missing Ohio plane Freedom Caucus member to bring up bill on impeaching IRS chief GOP seeks to make it 52 MORE, former Rep. Jeff Landry and Chas Roemer, son of former Louisiana Gov. Buddy Roemer, have not yet ruled out a bid.

Fleming told The Hill that Cassidy's decision to enter the race had not dissuaded him, and that he's still considering running.

"It’s imperative that Republicans have a strong conservative candidate to run against Mary Landrieu. We had the chance to see her on the record with the votes she cast in March and it’s abundantly clear that she’s an Obama liberal who is completely out of touch with Louisiana values. I haven’t ruled anything out. The polling I’ve done has made it clear that a conservative Republican can defeat Mary Landrieu. So, whether it’s Bill or I, the critical issue is that Louisianians have a distinct choice," he said.

Cassidy is the least conservative of the three former and current lawmakers to be considering a run, as measured by the Club for Growth's scorecard and National Journal's vote rankings. That record could open him up to a primary challenge from the right.

But his formidable fundraising abilities — he currently has more than $2 million cash on hand for his bid — may dissuade any potential challengers from entering the race.

Stephen Handwerk, executive director of the Louisiana Democratic Party, noted Cassidy's vote against Hurricane Sandy relief as part of the reason Louisiana voters will reject him.

"Bill Cassidy has spent his time in Congress fighting for extremists in Washington at the expense of the people of Louisiana. He is going to have a hard time convincing people in Louisiana that he has their best interests at heart when he repeatedly votes against hurricane protection and recovery funding and votes to give tax cuts to millionaires," he said in a statement.

Landrieu remains one of the most vulnerable Democrats going into 2014.  She is running for reelection in a state that President Obama lost by more than 15 percentage points in 2012.

Brooke Hougesen, a spokesperson for the National Republican Senatorial Committee, sought to tie Landrieu to Obama in a statement following Cassidy's announcement.

"Over the last 15 years, Senator Landrieu has lost touch with Louisiana and transformed into a Washington Liberal, evidenced by her consistent support for President Obama’s most controversial initiatives like ObamaCare and massive tax hikes, which is why voters will oppose her in 2014," she said.

Republicans in the state plan to make the president the centerpiece of their attacks on Landrieu. In his announcement video, Cassidy will highlight Landrieu's connection to the president, according to The Associated Press, which first reported the news of his run.

--This piece was updated at 5:45 p.m. to reflect statements from Fleming, the NRSC and the Louisiana Democratic Party.