Multiple US service members were killed when a suicide bomber blew himself up at a restaurant in the key city of Manbij in Syria's north, the deadliest attack against US forces since they first deployed in Syria in 2015. "We are still gathering information and will share additional details at a later time", the tweet from Operation Inherent Resolve said.
The Kurdish Hawar news agency, based in northern Syria, said three Americans were killed.
The Islamic State group claimed responsibility for the morning attack, which local groups said killed 16 people in the US -patrolled town of Manbij.
In March past year, a roadside bomb killed two coalition personnel, an American and a Briton, and wounded five in Manbij.
With no set date for a United States withdrawal, National Security Adviser John Bolton has said that it would only occur after the USA had drawn up a contingency plan with its allies in the region to protect Kurdish fighters.
Last week, the US military began pulling out equipment from the northeast into neighbouring Iraq.
The U.S. -backed Kurdish fighters for the YPG militia that is allied to the fighters holding Manbij last month invited Assad into the area around the town to forestall a potential Turkish assault. Other videos showed helicopters flying over the area reportedly to pick up victims.
Roughly 2,000 American troops remain in Syria, where they have operated since intervening in 2014.
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IS no longer holds fixed positions in the Manbij area and is now defending its very last pocket of land against US-backed Kurdish-led forces in eastern Syria. The attack will inevitably raise questions about how strong the group remains, and could create public pressure for European countries including France to withdraw if their forces died in the attack.
Amaq - ISIS's media wing - claimed that the attacker used a suicide vest to strike at coalition forces near a resteraunt in the flashpoint Kurdish-held city.
Vice President Mike Pence is facing harsh criticism after he claimed ISIS had been defeated on the same day that the terrorist group killed American soldiers in Syria.
Photos and videos showed damage to a restaurant, vehicles and other nearby buildings. In a brief statement, White House spokeswoman Sarah Sanders said, "The President has been fully briefed and we will continue to monitor the ongoing situation in Syria". Last week, White House National Security Adviser John Bolton went to Ankara seeking agreements on conditions for the USA withdrawal and guarantees not to attack the SDF, but Erdogan refused to meet with him.
The announcement rattled allies in the region and high-ranking U.S. officials, including Secretary of Defense Jim Mattis, who quit his post.
Turkish President Recep Tayyip Erdogan said he had a "quite positive" telephone conversation with Trump late on Monday where he reaffirmed that "a 20-mile (30 kilometer) security zone along the Syrian border. will be set up by us".
Children stand between the rubble, rebel-held Douma, Syria.
Wednesday's attack took place at a restaurant near Manbij's main market.