The Syrian Observatory for Human Rights said on Friday that the death toll from an air strike in eastern Syria overnight had climbed to 54, including IS fighters and 28 civilians, reports Agencies.
The air strike hit an area a few kilometers (miles) from the border with Iraq.
Most of the civilians were Iraqi, Observatory Director Rami Abdulrahman said by phone.
The raid late Thursday hit a "gathering of civilians" at an ice factory near the village of Al-Soussa near the Iraqi border, the Britain-based Syrian Observatory for Human Rights said.
It was not immediately clear if the strike was carried out by an Iraqi plane or by one of the US-led coalition fighting IS, the monitor said.
Iraqi warplanes have recently carried out strikes against IS in eastern Syria, while coalition aircraft have been supporting Kurdish-led fighters battling the jihadists.
State news agency SANA reported the strike late Thursday, saying more than 30 civilians were killed and accusing the US-led coalition of carrying it out.
The coalition was not immediately available for comment.
IS fighters swept across Syria and Iraq in 2014, declaring a cross-border "caliphate" in areas they controlled.
They have since lost most of that territory to various offensives, but still retain pockets of land in Syria including in the country's vast Badiya desert and in Deir Ezzor.
IS fighters have faced two separate offensives in Deir Ezzor on either side of the Euphrates River that cuts through the province.
Russia-backed regime forces have pushed back the jihadists on the western side of the Euphrates, while the US-backed Syrian Democratic Forces alliance has battled them to its east.
Al-Soussa lies to the east of the Euphrates River, in a pocket of territory still held by the jihadists.
IS fighters have been expelled from most urban centres in Syria, but analysts say they have retained their ability to pounce from the desert.
Last month, an IS incursion into the town of Albu Kamal on the west of the Euphrates left dozens of pro-regime fighters dead.
Attacks spiked after the jihadists were evacuated from their last bastion outside Damascus in May, many heading to the Badiya desert, the Observatory said.
IS also has a presence in the northwestern province of Idlib, as well as in the southwestern province of Daraa where it has been battling opposition fighters in recent days.