The Britain-based monitoring group, which relies on a network of sources on the ground, said it had documented the deaths of 180,215 people.
Among them were 58,805 civilians, including 9,428 children and 6,036 women.
The group said 49,699 members of the armed opposition had been killed, among them fighters from jihadist groups like Al-Qaeda affiliate Al-Nusra Front and the Islamic State. It did not break the figures down further.
The new toll includes 66,365 regime forces -- 40,438 from the military, and 25,927 members of a pro-regime militia.
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The toll also includes 2,931 unidentified people whose deaths the Observatory has confirmed without being able to record their identities.
The conflict in Syria erupted in March 2011, with peaceful anti-government protests that the authorities responded to with force.
It has also displaced nearly half the country's population.