Mr Santos said the US should consider its long-term ties with Colombia
Colombia's ties with the US could be severely damaged if Congress does not approve a planned free trade deal, the country's vice-president has warned.
Francisco Santos Calderon told the BBC that a US failure to sign the pact would be a "slap in the face" to a strong ally.
The trade deal was signed two years ago by leaders of the two nations.
But US Democrats oppose the deal and have used their Congressional majority to block its passage.
The Colombian government feels it deserves favourable trade terms with the US after years of staunch support in the fight against drug trafficking, says the BBC's Greg Morsbach.
But American opponents of the deal argue jobs would be put at risk if cheap Colombian imports flood onto the US markets.
Others have flagged up Colombia's questionable human rights record, saying the US should do less not more business with Colombia.
Mr Santos told the BBC that he did not believe that the deal would be passed during the remaining days of the Bush administration - and that he was not optimistic for its future under President-elect Barack Obama.
He said it was critical that the incoming administration saw US-Colombia relations "not in the context of what special interest groups want but in the light of our long-term relationship".
"Not approving the free trade agreement would be certainly a slap in the face to the strongest strategic ally that the US has in the continent," he said.
But Mr Santos played down the significance of the "Plan Colombia" US military aid package - worth more than half a billion dollars annually - aimed at fighting drug production.
"I don't think this package is as important or relevant as it was six years ago," he said.
Colombia's drug enforcement budget alone cost $1bn a year, he said.
Some US Democrats are calling for more development - and less military - aid for Colombia. The US has also indicated that aid to Colombia could be cut because of the current financial crisis.
Mr Santo's remarks are a clear sign, our correspondent says, that Colombia's leaders are braced for a less generous White House.