The operation in the eastern province of Deir Ezzor on Sunday drew significant international attention after the Syrian Observatory for Human Rights, an independent monitor, said that 25 jihadists had been killed.
The defense official told AFP that only two Islamic State operatives died, including Abu Anas al-Iraqi, a "senior operative."
US television network ABC News quoted a counterterrorism official as saying he was a "top" IS leader.
The defense official, speaking on condition of anonymity, told AFP the two men had been killed in a vehicle on an isolated highway about 50 kilometers (30 miles) from the city of Deir Ezzor.
Deir Ezzor is Syria's second-biggest province after Homs. Since early 2015, jihadists have besieged the provincial capital, also called Deir Ezzor, home to some 200,000 people.
The official said the special operations raid was led by US forces, but commandos from other nations in the anti-IS coalition were present too.
According to ABC News, the men in the vehicle had opened fire at helicopters that were tailing it.
The choppers fired back, killing the vehicle's occupants, ABC said.