McCain, one of the first in Congress to call for military intervention in Libya, said the environment in Syria does not lend itself to a similar intervention there.
"Frankly, I don't see a military option," he said, citing the absence of an organized rebellion which the U.S. could support with air power. He instead called for stepped-up sanctions, something the Obama administration has started to pursue.
McCain, though, acknowledged the situation is "going very badly for the people of Syria" and said the clashes demonstrate that Syrian President Bashar Assad is no "reformer," as some in Washington used to claim.
"I think it's clear that Bashar Assad is willing to kill his own people," McCain said on CBS' "Face the Nation." "It's going to be a very bloody time, I'm afraid, in Syria."
The death toll in Syria has topped 500 as Assad's forces target demonstrators, mostly in the city of Daraa.
Former Democratic Rep. Jane Harman expressed concern Sunday that if nothing changes, the city could soon be the site of a massacre.
"We may be seeing in the next 24 hours a mass massacre in Daraa where Syrian troops are rolling in as we speak, and I think that is totally unacceptable in moral and strategic terms for us," she said on CNN's "State of the Union."
She said Syria remains "much more strategically important" to the United States than Libya. She said the unrest could become the scene of a "proxy war," considering it represents Iran's "back door into Lebanon and Israel."