Syrian state media, citing a military source, reported earlier that US-led coalition aircraft had bombed "one of our military positions" in eastern Syria, leading to deaths and injuries, but the US military denied carrying out strikes in the area.
The Syrian Observatory for Human Rights group originally said that 40 fighters loyal to Syrian President Bashar Assad were killed, but later stated that the death toll had risen to 52.
Other reports indicated the fatalities left by the strike were Iranian militia fighters.
The strike took place in al-Harra, southeast of Albu Kamal, Syrian state media said.
A commander in the military alliance backing Assad also told Reuters that drones, "probably American," had bombed positions of Iraqi factions between Albu Kamal and Tanf and Syrian military positions.
The claim, however, was flatly denied in the US. "No member of the US-led coalition carried out strikes near Albu Kamal," Major Josh Jacques, a US Central Command spokesman said.
The US-led coalition is supporting an alliance of Syrian Arab and Kurdish militia fighting Islamic State northeast of Albu Kamal.
The Syrian army, alongside allied Iran-backed militias including Lebanon's Hezbollah and Iraqi groups, drove Islamic State from Albu Kamal and its environs last year, but the jihadists have since staged attacks in the area.
US forces are also based in Tanf, southwest of Albu Kamal in the Syrian desert near the borders of Iraq and Jordan.
The Syrian army, alongside Iran-backed militias including Lebanon's Hezbollah and Iraqi groups, drove Islamic State from Albu Kamal and its environs last year, but the jihadists have since staged attacks in the area.