White House spokesman Josh Earnest stressed that Washington respects the right of Scots to decide their future in Thursday's referendum but hoped for a "strong, robust and united" partner.
The comments mirrored those by President Barack Obama as he stood side-by-side with British Prime Minister David Cameron in Brussels earlier this year.
But, coming three days before Scotland votes on whether to end the 300-year-old union with England, the remarks hint at US concern at a weakening of its key NATO and United Nations Security Council ally.
"We certainly respect the right of individual Scots to make a decision along these lines," he added.
"But ... We have an interest in seeing the United Kingdom remain strong, robust, united and an effective partner.