"What doesn't make sense is to take unilateral action right now," Panetta told the Senate Armed Services Committee about advising President Barack Obama to dispatch U.S. forces. "I've got to make very sure we know what the mission is ... achieving that mission at what price."
The panel's top Republican, Sen. John McCain of Arizona, said the estimated 7,500 dead and the bloodshed calls for U.S. leadership that a Democratic president, Bill Clinton, displayed during the Bosnian war in the 1990s and that Obama eventually showed on Libya last year.
"In past situations, America has led. We're not leading, Mr. Secretary," McCain told Panetta.
Testifying before the committee, Army Gen. Martin Dempsey and Panetta offered a cautionary note to the call by McCain to launch U.S. airstrikes against Assad's regime.
"This terrible situation has no simple answers," Panetta told the panel.
Obama has resisted calls to step into the turmoil in Syria to stop Assad's crackdown on protesters. He told a news conference Tuesday that the international community has not been able to muster a campaign against Syria like the one in Libya that ousted Moammar Gadhafi last year.
"For us to take military action unilaterally, as some have suggested, or to think that somehow there is some simple solution, I think is a mistake," Obama said. "What happened in Libya was we mobilized the international community, had a U.N. Security Council mandate, had the full cooperation of the region, Arab states, and we knew that we could execute very effectively in a relatively short period of time. This is a much more complicated situation."
Obama's strategy has been to use sanctions and international diplomatic isolation to pressure Assad into handing over power.
The Pentagon chief said the United States is currently focused on isolating the Assad regime diplomatically and politically, arguing that it has lost all legitimacy for killing its own people. He left open the possibility of military action, saying the Obama administration continues to assess the situation and would adjust its strategy as necessary.
Dempsey said among the military options are enforcement of a no-fly zone and humanitarian relief. He said a long-term, sustained air campaign would pose a challenge because Syria's air defenses are five times more sophisticated than Libya's. He said Syria's chemical and biological weapons stockpile is 100 times larger than Libya's.
"We also need to be alert to extremists, who may return to well-trod ratlines running through Damascus, and other hostile actors, including Iran, which has been exploiting the situation and expanding its support to the regime," Dempsey said. "And we need to be especially alert to the fate of Syria's chemical and biological weapons. They need to stay exactly where they are."
McCain, along with Sens. Lindsey Graham, R-S.C., and Joe Lieberman, I-Conn., have called for U.S. military involvement. But the issue has divided Republicans, with House Speaker John Boehner, R-Ohio, insisting on Tuesday that the situation is too muddled and U.S. military involvement would be premature.
Committee Chairman Carl Levin, D-Mich., said there is no consensus on how to get Assad to leave.