Rebels and jihadists pressed offensives inside the capital Damascus and the central province of Hama, just a day before new UN-brokered peace talks open in Geneva.
Years of diplomatic efforts have failed to end Syria's raging six-year conflict, which began with protests against President Bashar al-Assad.
The war has killed more than 320,000 people, sparked a major refugee crisis, and dragged in world powers including the US-led air coalition bombing Syria's jihadists since 2014.
The monitor said today that the strike hit a school being used as a temporary shelter for displaced families, about 30 kilometres west of IS-held Raqa city.
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"We can now confirm that 33 people were killed, and they were displaced civilians from Raqa, Aleppo and Homs," said Observatory head Rami Abdel Rahman.
"They're still pulling bodies out of the rubble until now. Only two people were pulled out alive," Abdel Rahman told AFP.
"Raqa is Being Slaughtered Silently," an activist group that publishes news from IS-held territory in Syria, blamed the coalition for the strike. "The school that was targeted hosts nearly 50 displaced families," it said.
Top officials from the 68-nation alliance are set to meet in Washington to hear more about a revised plan drafted by the Pentagon and presented to US President Donald Trump in February.
Earlier this month, the coalition said its campaign in Syria and Iraq had unintentionally killed at least 220 civilians, but monitors say the real number is far higher.
In addition to bombing raids by the coalition, Russia is carrying out strikes in support of its ally Assad and Turkey has provided air cover for rebel groups in the north.
This week, rebels and allied jihadists launched two surprise offensives on government positions in Damascus and central Hama province, opposition groups and the Observatory said. In Damascus, anti-regime factions are battling to link up territory they hold in the eastern district of Jobar with their encircled forces in the Qabun neighbourhood to the north.
Clashes continued today as at least nine air strikes pounded rebel positions, the Observatory said.
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