Presumptive Democratic presidential nominee Hillary Clinton could reveal her running mate as early as Friday, according to US media.
Her announcement would come ahead of the Democratic National Convention, which is due to begin on Monday in Philadelphia.
Senator Elizabeth Warren, a favourite choice among Democrats, has said she was "probably not" the choice.
Virginia Senator Tim Kaine has emerged as a leading contender for the role.
The former secretary of state may reveal her vice-presidential pick on the campaign trail in the key battleground state of Florida.
Mrs Clinton is expected to attend a rally at Florida International University on Saturday, where her newly minted running mate could also make an appearance.
Secretary of Agriculture Tom Vilsack, Labour Secretary Tom Perez and New Jersey Senator Cory Booker were also reportedly on the short list for the job.
However, the Clinton campaign has cautioned that the likely nominee has not yet made a final decision.
Mrs Clinton's announcement would come on the heels of Republican rival Donald Trump's address at the party's convention.
Mr Trump formally accepted the nomination while speaking for more than an hour on Thursday, vowing to fight the multiple threats facing the US, including crime, immigration and global terrorism.
Mrs Clinton was swift to respond to the billionaire's remarks, pushing back on his claims that crime was on the rise as well as blasting his play on her slogan.
The Democratic candidate's campaign has frequently used the line "I'm With Her."
Mr Trump told delegates in Cleveland that he chose to recite a different pledge: "I'm With You."
"I am your voice," Mr Trump said. "I'm With You, and I will fight for you, and I will win for you."
Mrs Clinton quickly fired back on Twitter to describe what she believed the phrase really meant.
The announcement of a vice-presidential pick could help build anticipation for the Democratic National Convention, where Mrs Clinton will formally accept the party's nomination.
However, the Clinton campaign has remained tight-lipped about its search for a vice-president.
Senator Kaine, the former governor of Virginia, could be a boon to Mrs Clinton among white male voters and independents.
The 58-year-old was elected to the Senate in 2012 after serving as the governor of Virginia from 2006 to 2010.
Mr Kaine is fluent in Spanish and a proponent of free trade, including the Trans-Pacific Partnership and the North American Free Trade Agreement (Nafta), which Mr Trump has railed against throughout his campaign.
Agriculture Secretary Vilsack is also considered a top contender for the number two spot.
Mr Vilsack, 65, is a former governor of Iowa and has been President Barack Obama's agriculture secretary since 2009.
Senator Booker, the former mayor of Newark, New Jersey, would be the first African-American vice presidential nominee.
The New Jersey senator, who boasts a massive online following, appeared with other Democrats in Cleveland after the Republican National Convention ended.
"I'm happy to do what the coach asks me to do," said Booker, referring to Mrs Clinton.
Labour Secretary Perez has also supported the Trans-Pacific Partnership but also has criticised Nafta.
He would become the first Hispanic candidate to take on the role for the Democratic party.