The Syrian Observatory for Human Rights said four senior Syrian army officers were among the troops and allied militiamen killed in the desert east of Homs province over the past 48 hours.
The Amaq propaganda arm of IS, which lost the last vestige of its "caliphate" to Kurdish-led forces last month but retains desert and mountain hideouts in both Syria and Iraq, said its fighters carried out the operation.
Another eight soldiers and militiamen, including two officers, were killed in a separate attack in neighbouring Deir az-Zour province on Thursday night, the Observatory said.
The attack targeted a desert village south of the city of Mayadeen, upstream from the stretch of the Euphrates Valley where IS made a desperate last stand for its "caliphate", the Britain-based war monitor said.
Observatory chief Rami Abdel Rahman described it as the "biggest attack and the highest death toll among regime forces since the caliphate was declared defeated".
Six IS fighters were killed in the clashes, the Observatory said.
Amaq said that IS had launched its assault on Thursday evening after government forces tried to track down its fighters.
The vast Syrian desert, known in Arabic as the Badia, stretches all the way from the capital Damascus and the cities of Homs and Hama to its north to the Euphrates Valley near the Iraq border, where the "caliphate" was defeated in the village of Baghouz last month.
Commanders of the US-led coalition, which provided air and artillery support for the Kurdish-led operation, have warned repeatedly that the jihadists' loss of their last piece of territory did not mean their elimination as a fighting force.
Analysts have said that continuing search and destroy operations by the multiple alliances lined up against the jihadists would be necessary to prevent them mounting a comeback from their desert hideouts.
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