Some 90 guards at the Shaer gas field and 21 ISIS fighters died in the attack, and another 270 guards, government forces and militia members loyal to Syrian President Bashar al-Assad were missing, taken prisoner or wounded, Al-Jazeera reported.
"Since the beginning of the year there have been clashes between the Islamic State and the regime in some areas, but these are the largest," the Observatory's director Rami Abdel Rahman said.
Earlier this month, the extremist Sunni militants took over another oil field in eastern Syria's Deir Ezzor province. It's the country's largest oil field, producing some 75,000 barrels of oil per day.
ISIS overtook that field without a single shot being fired, and no one was injured or killed in the incident.
ISIS is among the groups fighting the Syrian government in its four-year civil war, and has undertaken the capture of territory in Syria and Iraq in recent months, claiming it controls the land from Aleppo, Syria, eastward to Diyala province in eastern Iraq.