Syria threatens to 'destroy' Turkish fighter jets
"We warn that the Syrian Air Force is ready to destroy Turkish air targets in the skies of Syria," Mekdad told reporters, according to Syria's official SANA news agency.
"We warn the Turkish leaders that if they start fighting in the region of Afrin, it will be seen as an aggression by the Turkish army against the sovereignty of Syria," he added.
Afrin is among the areas Turkey has said it will attack in northern Syria to target the Kurdish People's Protection Units (YPG) militia.
Ankara accuses the YPG of being a branch of the outlawed Kurdistan Workers' Party (PKK) that has waged an insurgency in Turkey since 1984.
The US-led coalition fighting the Islamic State group said at the weekend it was working to create a 30,000-strong border security force in northern Syria.
Ankara immediately objected, fearing the new force would be comprised of the YPG.
President Recep Tayyip Erdogan said this week that Turkey had to "nip this terror army in the bud".
The United States later backtracked, insisting it does not intend to create an army or conventional border guards.
Erdogan said on Monday that Turkey would soon begin an operation against towns in Syria controlled by Kurdish militia, calling the areas "nests" of terror.
"Tomorrow, (or) the day after, (or) within a short period, we will get rid of terror nests one-by-one in Syria starting with Afrin and Manbij" in northern Syria, he said in a televised speech.
Syria's main Kurdish political party on Wednesday called on the UN Security Council to act quickly to ensure the safety of Kurdish-controlled territories.
Tanks have amassed near the border with Syria, while Turkish media reported that medical personnel in Kilis, a Turkish town across the border from Afrin, were asked not to take leave, apparently in anticipation of military operations.