On Sept. 18, Scotland will hold a referendum on whether to break away from the United Kingdom and declare independence from its 307-year-old union with England.
"I would hate to have you lose Scotland," said Clinton, widely considered the Democratic front-runner if she enters the 2016 U.S. presidential race.
Her comments came a week after Obama said the United States wanted a "united" partner, but that the Scottish vote was for Scots to decide.
Obama also made it clear he would prefer Britain to stay inside the European Union, saying it was encouraging for Washington to know its ally had "a seat at table in the larger European project."