The four staff of the Union of Syrian Medical Relief Organisations (UOSSM) were in two ambulances that had been called to the clinic to take some patients for more specialised treatment, the group said.
The clinic in the village of Khan Tuman was completely levelled in the 11:00 PM strike and more dead were feared to be buried under the rubble, the group added.
"The building has three floors, including a basement. Because of the intensity of the bombardment, the three storeys collapsed and are completely destroyed," the groups' hospitals and trauma director for the area, Ahmed Dbais, said in a statement.
Khan Tuman is near Orum al-Kubrah, the town where an attack on aid trucks and a warehouse killed around 20 civilians on Monday, triggering a war of words between major powers after Washington accused Moscow of responsibility.
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According to the World Heath Organization, Syria is the most dangerous country in the world for health professionals with 135 strikes on clinics and hospitals last year.
The head of UOSSM France, Dr Ziad Alissa, condemned the "unacceptable" attack on the group's clinic and staff.
"Deliberately targeting humanitarian workers and medical professionals is a clear violation of international humanitarian law," he said.
The UOSSM is a medical aid group originally founded by Syrian expatriates but now international.