"The number of Al-Nusra Front and rebel fighters killed in battles (Saturday) against ISIL in the strategic town of Markada in the south of Hasake province has risen to 39," said the Syrian Observatory for Human Rights.
The group said ISIL lost 13 of its fighters as it took total control of Markada.
"Markada is important because it provides ISIL with a supply route from Iraq into the road linking Hasake to Deir Ezzor," said the Observatory.
ISIL has been fighting a war against rebels, including the Al-Qaeda affiliate Al-Nusra Front, since January across large swathes of western, northern and eastern Syria.
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Once allied to ISIL, Syria's rebels and Al-Nusra turned against the jihadists, angered by their quest for hegemony and abuses.
While ISIL has withdrawn from much of the west and north of Syria, it has held its ground firmly in the east, near the Iraqi border.
On another front, fighting raged in flashpoints of Latakia province on the Mediterranean coastline, where rebels and Al-Nusra Front began a surprise offensive against the army last week.
Since late last week, the rebels have taken over a key border crossing with Turkey at Kasab and a handful of villages.
Today, the fighting was focused around the village of Qustul Maaf and the Nisr mountain, which is surrounded by rebels.
The battle in Latakia has killed some 300 fighters on both sides, the Observatory said, including 180 army and paramilitary troops loyal to Assad's regime.
More than 146,000 people have died in Syria's three-year war and nearly half the country's population have fled their homes.