A U.S.-led coalition airstrike on the eastern Syrian town of Mayadeen early Friday killed at least 80 relatives of ISIS fighters, activists told AFP.
"The toll includes 33 children. They were families seeking refuge in the town's municipal building," said Rami Abdel Rahman, head of the Syrian Observatory for Human Rights.
"This is the highest toll for relatives of ISIS members in Syria," Abdel Rahman told AFP.
The latest strike came as the United Nations urged all nations bombing extremists targets in Syria to better distinguish between civilian and military targets.
U.N. human rights chief Zeid Ra'ad Al Hussein said "all states" whose air forces are active in the anti-ISIS missions needed "to take much greater care to distinguish between legitimate military targets and civilians."
The Britain-based Observatory gathered information from civilian and medical sources on the ground in ISIS-held Mayadeen, which was facing its third day of fierce bombing.
According to the Observatory, 37 civilians were killed in coalition raids on the town Thursday night, including 13 children, and another 15 had been killed in coalition strikes Wednesday.
The 68-member coalition began bombing ISIS targets in Iraq in the summer of 2014, and expanded their operations to Syria on Sept. 23 of that year.
This week, the Observatory reported the highest monthly civilian death toll for the coalition's operations in Syria.
Between April 23 and May 23 of this year, coalition strikes killed a total of 225 civilians in Syria, including dozens of children.
The U.S.-led alliance is backing twin ground offensives against ISIS' last main bastion cities: Raqa in northern Syria and Mosul in neighboring Iraq.
On Thursday, a Pentagon investigation concluded that at least 105 civilians died in an anti-extremist airstrike on an ISIS weapons cache in Mosul in March.
Prior to the new revelation, the U.S. military had said coalition airstrikes in Iraq and Syria had "unintentionally" killed a total of 352 civilians since 2014