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US Secretary of State Antony Blinken and Secretary of Defence Lloyd Austin will arrive in Belgium on Tuesday to discuss Ukraine and Afghanistan.
Tension is mounting between Russia and Nato over Ukraine and the deadline for international forces to leave Afghanistan is looming.
Mr Blinken is set to leave Washington for Brussels on Monday evening.
He will join Mr Austin “to consult with our Nato allies and partners on a range of shared priorities”, the US State Department said.
Ukraine and Afghanistan are expected to be priorities on the delegation's agenda and in meetings with their Nato counterparts, a US official told The National.
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Mr Blinken and Mr Austen are expected to meet Nato Secretary General Jens Stoltenberg, the official said.
On Monday, Mr Blinken called Mr Stoltenberg hours before the trip stressing the need for Russia to "cease its military build-up."
"Secretary Blinken and Secretary General Stoltenberg discussed a range of issues, including the immediate need for Russia to cease its aggressive military build-up along Ukraine’s borders and in occupied Crimea. They also discussed the prospects for advancing peace in Afghanistan as well as plans for the upcoming Nato summit," the US readout said.
The trip to Brussels, Mr Blinken’s second in less than a month, highlights increased US-Nato co-operation and the challenge that Moscow’s actions pose to the alliance as it continues to amass troops on the border with Ukraine.
“President Biden’s been very clear about this. If Russia acts recklessly or aggressively, there will be costs, there will be consequences,” Mr Blinken told NBC on Sunday. “We can’t go back to four years ago or six years ago or eight years ago – pick your year … The president, before he was elected, made clear that, again, when it comes to Russia’s actions, there’ll be costs and consequences if it acts recklessly and aggressively, and you can hold him to that word.”
In the past two weeks and since the military build-up started, Mr Blinken and Mr Austin have spoken with their counterparts in Ukraine, Britain, Germany and France about the “provocations”. But Russia has been defiant and undeterred by US-Nato warnings.
On Friday, Kremlin spokesman Dmitry Peskov defended Russian military build-up as something that is in Moscow's national security interest and in reaction to actions taken by Ukraine.
“If a civil war – a full-scale military action – resumes near our borders, that would threaten the Russian Federation’s security,” he said. “The growth of tension, the escalation of tension in the south-east of Ukraine, determines the measures that Russia is taking to ensure its security.”
Mr Peskov said that the current dynamics “create the danger of a resumption of full-scale hostilities”.
Another pressing foreign policy priority on Mr Blinken’s trip will be the troop presence in Afghanistan.
According to an agreement made between former president Donald Trump and the Taliban, all foreign forces are expected to leave the country by May 1. But Mr Biden has not committed to this deadline and the Nato alliance has not made a final decision on when members will withdraw their troops.
"It's going to be hard to meet the May 1 deadline," Mr Biden said last month. "Just in terms of tactical reasons, it's hard to get those troops out … if we leave, we're going to do so in a safe and orderly way."