Syrian Defence Minister Daoud Rajha was killed in a suicide bombing in Damascus Wednesday, just hours before a crucial UN vote on the violence-plagued Middle East country, state television reported.
The blast occurred during a meeting of ministers and security officials at national security headquarters.
President Bashar al-Assad's brother-in-law, Deputy Defence Minister Assef Shawkat, was also fatally injured in the attack, the Hezbollah's al-Manar TV said.
Several other top officials, including the interior minister, are in a critical condition, TV reports said.
The attack came as heavy fighting raged in the capital.
The rebel Free Syria Army said earlier this week it had launched the final battle for Damascus, which had so far seen little of the violence that has claimed thousands of lives across Syria.
The 15-member UN Security Council will vote later Wednesday on a new Western-backed resolution on Syria which could lead to tough new sanctions against Assad's regime.
Russia has said it will block the resolution and has called for all sides in the conflict to implement UN special envoy Kofi Annan's floundering peace plan.