Air strikes on Thursday and Friday on the village of Sousa killed 41 civilians, 10 of them children, according to the Syrian Observatory for Human Rights.
The Britain-based monitor blamed the coalition, which is backing an offensive launched last month by a Kurdish-Arab alliance against IS’s last redoubt in the country’s east.
The majority of those killed in the strikes were family members of IS fighters, Observatory chief Rami Abdel Rahman told AFP on Sunday.
“Only six are Syrians, the others are mostly Iraqi,” he said.
The coalition said it did not carry out any bombing runs on Friday, but that a raid on Thursday targeted a mosque being used as a “command and control centre”.
“Our assessment is only ISIS fighters were present at the command centre at the time of the strike,” Colonel Sean Ryan said in response to questions from AFP sent by email.
He said “12 Daesh terrorists” were killed in the raid, using an Arabic acronym to refer to IS.
“If there are credible claims of possible civilian casualties, they will be investigated,” he added.
According to the Observatory, Thursday’s strike killed 18 civilians, including seven children, all of whom were related to IS jihadists.
It said 11 IS fighters were also killed in the raid.
IS overran large swathes of Syria and neighbouring Iraq in 2014, proclaiming a “caliphate” across the land it controlled.
But the jihadist group has since lost most of it to various offensives in both countries.
In Syria, the group has seen its presence reduced to parts of the vast Badia desert and a pocket that includes Sousa in the eastern province of Deir ez-Zor along the border with Iraq.
Since 2014 the US-led coalition has acknowledged direct responsibility for more than 1,100 civilian deaths in Syria and Iraq, but rights groups put the number killed much higher.
The Syrian Observatory for Human Rights says coalition strikes in Syria alone have killed more than 3,300 civilians.
Syria’s war has killed more than 360,000 people since it erupted in 2011 with the brutal repression of anti-government protests.
