The deaths came in yesterday attacks launched as the jihadist group faces a Russian-backed regime offensive against some of its last bastions.
The extremist group claimed the attacks against several positions south of the town of Sukhna in central Homs province, saying its fighters had killed dozens of regime troops.
The attacks come a day after IS released what it said was an audio recording of its leader Abu Bakr al-Baghdadi, the first in a year, in which he urged resistance.
Yesterday's attacks targeted government forces around Deir Ezzor and on their supply lines through the Sukhna area from the west, the Observatory said.
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"The first attacks were carried out against checkpoints manned by loyalist troops in Al-Shula," a village near Deir Ezzor, the Britain-based monitoring group said.
"IS then carried out a series of attacks against checkpoints along the length of the motorway from Al-Shula to south of Sukhna."
State news agency SANA said the army had "inflicted heavy losses on the ranks of the terrorists", adding that units were "currently working to clear remaining Daesh terrorists from the area and secure the highway for traffic".
The Observatory said at least 45 IS fighters had been killed in the fighting.
The attacks by the jihadists came as they face multiple offensives against the last bastions of their self-proclaimed caliphate.