Sen. John McCain, R-Ariz., said sanctions will be tough but that Iran poses a greater danger to the United States than Iraq at this point and must be contained.
"If the price of oil has to go up, then that's a consequence we would have to suffer," McCain said on Face the Nation.
Iran restarted its research at a nuclear facility last week after a two-year freeze. Iran has always insisted it's just trying to build a nuclear power industry, but by hiding a uranium enrichment program for almost two decades, it convinced much of the world it is really trying to build a bomb, reports CBS News correspondent Richard Roth.
The Bush administration says Iran wants to make nuclear arms and is pursuing harsh penalties through the United Nations Security Council.
But it's unclear if the U.S. has support from other Security Council members, particularly Russia and China. Iran is OPEC's second-largest producer, and trade restrictions could increase already high prices across the globe, even for nations that don't import oil from Iran.
Sen. Chuck Schumer, D-N.Y., said Bush should do whatever he can to get support from Russia and China.
"They need stuff from us," Schumer said on "Fox News Sunday. "They need trade. They need all kinds of assistance. We ought to play hardball with them."
McCain said it would be "abominable" for Russia and China to vote against sanctions. In that case, he said the U.S. should pursue them anyway with other nations that are willing to support them.
Sen. Trent Lott, R-Miss., said penalties should be imposed as a response to Iran's "irresponsible" behavior. He pointed to Iran's announcement Sunday that it will hold a conference to examine evidence of the Holocaust. Iranian President Mahmoud Ahmadinejad has called the Holocaust a "myth" and called for Israel to be wiped from the face of the earth.
"We cannot be intimidated by economic threats from their side," Lott said. "At the minimum, we should go to the U.N. Security Council and we should impose economic sanctions unless there is some dramatic change in the Iranian position."
Sen. Evan Bayh, D-Ind., said President Bush should have dealt with threats from Iran years ago. He said Iran is the foremost sponsor of terrorism in the world and a "force for instability and death."
"I'm glad the president is finally speaking out about this, but for four long years they have ignored this problem," Bayh told CNN's "Late Edition." "It has brought us to the position that we're in today. And it has undermined the national security interests of the United States."
The senators agreed that the United States should pursue penalties and diplomatic options before taking military action against Iran. They also agreed that Iran poses one of the most serious threats to the world since the Cold War.
"I don't think it's a stretch to say that if the Iranians had a nuclear missile that this president might well use it against Israel," said Sen. Dianne Feinstein, D-Calif., said on Face the Nation.