Activists say the students were leaving their school in Eastern Ghouta when a shell landed at the gate.
Four Syrian children are reported to have been killed today when their school was bombed.
Activists say a shell fired by government forces landed at the gate of the school in Jisreen, a town in the Eastern Ghouta area.
The attack comes two days after schoolchildren fled when a kindergarten in the nearby town of Kfar Batna was bombed. Video showed them running terrified into surrounding streets.
Today's attack in rebel-held Jisreen, outside the city of Damascus, was reported by the Ghouta Media Center and a Syrian human rights group.
"A shell fired by regime troops hit the entrance of a school in Jisreen just as children were leaving it, killing five people including four schoolchildren," the head of the British-based Syrian Observatory for Human Rights, Rami Abdel Rahman, said.
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Parts of Eastern Ghouta - including Jisreen - have been under siege from government forces since 2013.
Residents have been warning of a mounting hunger crisis and doctors said they are seeing dozens of malnourished children every day.
Yesterday the first convoy of aid for over a year went into Eastern Ghouta.
The joint United Nations-Syrian Arab Red Crescent mission saw 49 trucks carry 8000 food parcels and a similar number of bags of flour, medicine, medical supplies and other nutritional materials.
Schools should be places of safety for children. But classrooms and children have been the target of many attacks since the Syrian conflict began more than six years ago.