With military backing from Russian Federation since 2015, President Bashar al-Assad's government has made huge gains against the jihadists and rebels, and now controls nearly two-thirds of the country.
An apparent suicide bombing hit the Kurdish-controlled northern Syrian city of Manbij during a "routine" US-led coalition patrol, killing several United States troops and civilians.
"An explosion hit near a restaurant, targeting the Americans, and there were some forces from the Manbij Military Council with them", one said.
The US-led coalition has confirmed that Americans were killed in the attack, though it is not clear how many.
Doctors in Manbij told VOA two US soldiers were killed instantly. This official also said that the suicide bomber deliberately approached forces before detonating his device.
A total of 16 people including nine civilians died in the blast according to the British-based Syrian Observatory for Human Rights.
White House spokeswoman Sarah Sanders said President Donald Trump has been briefed on the situation.
Last month, Mr Trump made the surprise announcement that he would withdraw all 2,000 USA troops from Syria, concluding that IS had been defeated.
The bombing comes as Syrian Kurds present in areas around Manbij reject any Turkish presence in a planned "safe zone" to include Kurdish-held areas along the frontier.
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"We are bringing our troops home", Pence said in an address to 180 USA ambassadors and chiefs of missions overseas gathered for a conference in Washington.
He said the American President won't halt the withdrawal because it would mean ISIS wins.
Withdrawing the USA troops "set in motion enthusiasm by the enemy we're fighting", said Graham, chairman of the Judiciary Committee.
"I would hope the president would look long and hard at where he's headed in Syria", Graham added.
'I'm glad you mentioned Iraq and other places where we're fighting to help people, ' Graham said at the hearing about Trump's attorney general nominee William Barr.
The Islamic State has claimed responsibility for a suicide attack in Syria, which took the lives of at least 20 people.
"The collective discipline of ISIL is intact", the report said, using another of the terror group's acronyms.
"A suicide attack carried out with explosives vest hit an global coalition patrol in the city of Manbij", the terror group's propaganda arm Amaq said.
"While it may not hold territory, it certainly has battle-hardened fighters and facilitators who have blended back into the local population", he said.
USA troops deployed to the country are training and advising local partner forces battling ISIS.
Witness said the attacker had targeted the patrol and the militia group claimed on Facebook there was preliminary information of injuries.