US envoy for the coalition, Brett McGurk, appeared to blame regime forces for the civilian casualties.
Coalition disputes claims that its air strikes kill 40 in east Syria
The US-led anti-ISIS coalition hit back Sunday at reports its air strikes on the militant group's holdout in eastern Syria had killed civilians, appearing to blame their deaths on regime forces.
More than seven years into the country's civil war, multiple offensives have whittled down the swathes of Syrian territory ISIS once controlled to a small pocket in the eastern province of Deir Ezzor on the Iraqi border.
A Kurdish-led alliance backed by the coalition is battling to expel ISIS from that holdout, on the eastern bank of the Euphrates.
Russian-backed regime forces have been fighting the militants west of the river.
The Syrian Observatory for Human Rights said coalition strikes on Saturday killed 43 people, including 36 family members of ISIS fighters in the village of Abu al-Husn.
But the coalition denied that its air raids there had killed any non-combatants.
The US envoy for the coalition, Brett McGurk on Sunday appeared to blame regime forces stationed "across the river" for the civilian casualties.
"Reports of civilian casualties attributed to coalition strikes are false. All other forces should cease uncoordinated fires from across the river immediately," he said on Twitter.
In a statement late Saturday, the coalition reported 19 coalition strikes on ISIS targets "free of civilian presence" between late Friday and Saturday afternoon in the militant enclave, which includes the town of Hajin.
The coalition's "initial assessment following the strikes is that there was no evidence of civilians near the strikes", it said.
But the coalition "detected a total of ten additional strikes in the same area of Hajin that did not originate from the coalition or partner forces," it added.
It called "on all other actors to cease uncoordinated fires across the Euphrates."
The Observatory, a Britain-based war monitor, said regime forces and IS fighters exchanged fire across the river on Saturday, but pro-government shelling did not hit Abu al-Husn.
The US-led international coalition has consistently denied reports by the Observatory in recent days that its air raids have killed civilians.
It says it takes allegations of civilian casualties seriously and investigates each one thoroughly.
ISIS overran large swathes of Syria and neighbouring Iraq in 2014, proclaiming a "caliphate" in land it controlled.
But the militant group has since lost most of it to offensives by multiple forces in both countries.
On Saturday, Syrian regime forces retook control of the group's last holdout in the country's south as the militants retreated into the desert after months of fighting, the Observatory said.
Syria's war has killed more than 360,000 people since it erupted in 2011 with the brutal repression of anti-government protests.
Since 2014, the US-led coalition has acknowledged direct responsibility for over 1,100 civilian deaths in Syria and Iraq, but rights groups put the number much higher.