The Britain-based monitoring group, which relies on an extensive network of sources on the ground across Syria, said 353,935 people have been killed since March 15, 2011.
The Observatory, which tracks death tolls using a network of contacts inside Syria, said it had identified more than 350,000 of those killed, and the remainder were cases where it knew deaths had occurred but did not know the victims' names.
The conflict began after mass protests on March 15 2011, dragging in regional and global powers and forcing millions of people - more than half the pre-war population—to flee their homes.
About 85 percent of the dead were civilians killed by the forces of the Syrian government and its allies, the Observatory said. The Syrian military, joined by its ally Russia since 2015, has used air power extensively.
As the war approaches its eighth year, intense fighting continues in several areas, including eastern Ghouta near the capital Damascus and Afrin near the Turkish border.
Here is a breakdown of the deaths, according to the Observatory:
- 106,390 civilians, including 19,811 children and 12,513 women
- 63,820 regime soldiers
- 58,130 regime-allied and militia fighters (including 1,630 from Lebanon's Hezbollah and 7,686 from other foreign Shiite groups)
- 63,360 hardline Islamists and jihadists (including from the Islamic State group and a former Al-Qaeda affiliate)
- 62,039 fighters from other forces, including non-jihadist rebels, Kurdish forces and defected government soldiers
- 196 identity unknown but death documented
Reuters and AFP contributed to this report.