The former U.S. representative said she had decided against running for the seat being vacated by retiring Sen. Tim Johnson so she could spend more time with her family, The Hill reported.
Making the announcement on her Facebook page, Sandlin said "After carefully contemplating [a 2014 campaign], my family and I have concluded that the future should continue to be focused on the plans we laid last year at this time."
Polls conducted by the Democratic Senatorial Campaign Committee found Sandlin would have done well in a race against former Gov. Mike Rounds, the only Republican yet to announce.
Former two-time House candidate Rick Weiland is the only Democrat in the race. He announced last week.
Without mentioning Weiland, DSCC spokesman Justin Barasky said there would be "a strong Democratic candidate" who would be "a clear alternative to the dysfunction on the Republican side."
Sandlin's decision not to run cheered the National Republican Senatorial Committee, which noted Democrats had failed to recruit their chosen candidates in Kentucky and Georgia as well.
The DSCC was now "left facing the awkward situation of having to support their second, third and even 11th choice," NRSC communications director Brad Dayspring said.