White House deputy press secretary Josh Earnest said the administration was sorry to learn of Ahmed Moaz al-Khatib's resignation, calling him "a courageous and pragmatic leader who has a strong sense of Syrians' hopes and fears."
"The opposition has been well-served by his leadership and the Syrian people will continue to benefit from his service in whatever capacity he chooses to provide it," Earnest said.
"But it's important to underscore that leadership transitions are inevitable in any democratic process, and Khatib's announcement does not change the U.S. policy of support for the Syrian opposition and the Syrian Opposition Coalition.
"We support the coalition's vision for a tolerant, inclusive Syria that respects the rights of all Syrians. And the opposition to Assad's brutal rule is bigger than one person, and that movement will continue."
Earnest said the rebels' civil war "will continue unabated" and "the United States will continue to support their efforts."
Asked if the United States was considering further steps to beef up its support, Earnest reiterated the actions already taken and said they would continue.
Asked if Obama has been in touch with the leaders of Britain, France and Israel about the way forward with Syria, Earnest said he had no information to pass along other than to say the administration is working closely with its international partners and "other interested parties around the globe, who are trying to bring to an end the violence in Syria."
Earnest also said there was no new information about recent back-and-forth allegations of chemical weapons use in Syria.
Al-Khatib announced during the weekend he was resigning after an unproductive meeting with the European Union. He said he reached his limit following what he called two fruitless years of appealing to the international community for help in ending the nation's bloody civil war.
Al-Khatib said on Facebook he planned to address an Arab League summit in Qatar this week, the BBC reported.
Nizar al-Haraki, the coalition's envoy in Doha, said al-Khatib would lead the opposition delegation that is filling Syria's seat at the meeting. Syria's membership was suspended in November 2011.
Analysts said al-Khatib's resignation clouds the future of the Syrian opposition coalition.
Salman Shaikh of the Doha Brookings Center told several media outlets he thought al-Khatib's resignation "signifies the beginning of the end of this coalition."
The United Nations temporarily moved some of its international staff members working in Syria outside of the country because of security concerns, a U.N. spokesman said Monday.
Speaking at U.N. headquarters in New York, Martin Nesirky said a number of mortar shells fell on or near the grounds of the hotel in Damascus where U.N. personnel live.
"The United Nations Security Management Team has assessed the situation and decided to temporarily reduce the presence of international staff in Damascus due to security conditions. We are also exploring safer premises," Nesirky said.
The organization said there are about 100 international employees and 800 national employees in Damascus.
Rebel Free Syrian Army leader Riad Asaad was in stable condition in a Turkish hospital after losing a leg in a bomb attack on his car in eastern Syria Sunday, the BBC reported a group spokesman said.
No one had claimed responsibility for the attack on Asaad, which occurred several days after a video posted on YouTube showed him defending the al-Nusra Front and criticizing the main opposition coalition group
The United States designated the al-Nusra Front as a terrorist organization tied to al-Qaida but some rebels have said they have no problem fighting with the group against Syrian government forces.
"Nusra Front [fighters] are our brothers. They are 90 percent Syrians and the rest maybe from other Muslim countries," Asaad said in the video. "They haven't mistreated anyone in any way. We may have our own differences with them, but we respect them. Their mission is to serve the nation and the faith."
He also criticized the National Coalition for Syrian Revolutionary and Opposition Forces, the main opposition umbrella organization, saying, "The regime keeps killing our innocent civilians while the [coalition] is staying in fancy hotels, begging the world for financial support."
Asaad, a former colonel in the Syrian air force who defected in 2011, said rebels made a "big mistake" allowing "politicians to take over and divide our ranks."
A statement posted on Facebook by al-Khatib concerning the assassination attempt on Asaad spoke of "insidious schemes" against rebel leaders, The Guardian said in a blog on the events in Syria.
"The assassination attempt against Riad Asaad is an attempt to assassinate the free leaders of Syria," he wrote.
The United Nations has estimated more than 70,000 people have been killed and more than 3 million displaced since the uprising against Assad began in March 2011. About 1.1 million people have been forced to flee Syria.