But he's throwing his hat back in the ring for Cochran's seat.
"The American dream is alive and well in Mississippi", Hyde-Smith said, highlighting her support for Second Amendment rights and her pro-life stance.
Senator Thad Cochran is set to retire in less than 2 weeks, forcing Governor Phil Bryant to appoint a replacement. His choice to end his tenure as one of Mississippi's two Republican Senators has already created confusion and angst for the GOP, who are concerned about this year's Congressional midterm races.
She will need to run for election in November if she wishes to keep her seat.
Hyde-Smith, who previously served in the state Senate, has been agriculture commissioner since 2012.
He was most recently re-elected in 2014 and is the 10th-longest serving senator in US history.
Cochran, chair of the powerful Senate Appropriations Committee, announced his retirement for health reasons on March 5.
Phil Bryant is preparing to fill an upcoming vacancy in the U.S. Senate, and Republican sources tell The Associated Press that he will choose the state agriculture commissioner.
Now, there are concerns that Hyde-Smith will not be able to defeat Chris McDaniel, a hard-right state senator who also is running in the November 6 special election and has been sharply critical of McConnell. McDaniel will appear again in the Senate races coming up in November, even though the Republican Party is not quite sure how he plans to carry out his electoral ambitions. She promised to work closely with Mississippi's other Republican senator, Roger Wicker.
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Arguably, McDaniel's ultimate decision is the least of the Republican Party's worries for the upcoming mid-term elections.
POLITICO reported White House aides told Bryant that President Donald Trump wouldn't campaign for her. They recommended that, for now, the president should not endorse or campaign for Hyde-Smith should she get the appointment.
At issue is Hyde-Smith's past as a Democrat, though she describes herself as a "lifelong conservative".
The conversation was described by two White House aides with direct knowledge of the call. This trend is expected to continue for the upcoming midterm elections. "She was a Democrat until a few years ago", said one Republican official, granted anonymity to speak candidly.
Some Democratic voters simply fail to turn out for midterm and special elections, but we are seeing some shifts in this regard across the country. More than 100 Republican supporters signed McDaniel's letter.
Who will replace Cochran in the Senate?
"Cindy has always been a people person, has always wanted to help and do for everybody", Lowe, 67, said Wednesday in Brookhaven. The fact is, the DC establishment would rather let a Democrat have the seat than let a conservative win. The bill is now awaiting the governor's signature. Nevertheless, I am pleased that MS voters will have a clear choice in November for the open seat for United States Senate.