According to the activists, warplanes have struck positions of Iran-backed militias near Syria's border with Iraq.
According to the Syrian Observatory for Human Rights, a UK-based monitoring group, at least 18 Iranian and pro-Iranian fighters were killed.
It was not clear who carried out the overnight strikes in and around the town of Albu Kamal.
But Israel has carried out hundreds of attacks on Iranian-linked targets in Syria during the country's civil war.
It has sought to thwart what it calls Iran's "military entrenchment" in Syria and shipments of Iranian weapons to militant groups such as Hezbollah in Lebanon.
The Syrian Observatory for Human Rights cited its sources as saying the unidentified warplanes had bombed bases, arms depots and vehicles belonging to Iran-backed militias in al-Hizam al-Akhdar and other areas around Albu Kamal.
Omar Abu Layla, a Europe-based activist from the DeirEzzor 24 group, said powerful explosions were heard across the town, and that there was a "state of chaos and panic" among the militia fighters.