Six soldiers are missing believed killed in the single worst enemy attack on British troops in Afghanistan since operations began in 2001.
The servicemen were on patrol yesterday when their Warrior Armoured Fighting Vehicle was caught in an explosion.
Their deaths would take the total number of British forces personnel or Ministry of Defence civilians who have died while serving in the region to more than 400 since the US-led invasion in the wake of the 9/11 terror attacks.
Prime Minister David Cameron said the news was a "desperately sad day for our country".
Speaking in Downing Street, he added: "It is a reminder of the huge price that we are paying for the work we are doing in Afghanistan and the sacrifice that our troops have made and continue to make.
"I do believe it's important work for our national security right here at home but of course this work will increasingly be carried out by Afghan soldiers and we all want to see that transition take place.
"But today we should think of the families."
The servicemen - five from the 3rd Battalion the Yorkshire Regiment and one from the 1st Battalion The Duke of Lancaster's Regiment - were struck around 40km north of Lashkar Gah, in Helmand province.
Next of kin have been informed.
The incident represents the biggest single loss of British military personnel in the country since an RAF Nimrod crash which killed 14 people in 2006.
Defence Secretary Philip Hammond said he utterly condemned those responsible for the "tragic" event which brought home "the dangers that are faced on a daily basis" by those deployed in Afghanistan.
"My thoughts are with the families and friends of the six soldiers who are missing, believed killed and also with their colleagues, both in Afghanistan and the UK, whose brave work continues or is about to start," he added.
Chief of Defence Staff General Sir David Richards said he was "deeply saddened" by the news.
"My thoughts and prayers at this difficult time are with the families of those affected," he added.
The Nimrod explosion, on September 2 2006, came moments after mid-air refuelling when a fire broke out on the plane.
The aircraft blew apart as the crew tried to make an emergency descent to Kandahar airbase.
The crash prompted a scathing review which accused the MoD of sacrificing safety to cut costs.
An inquest in 2008 saw Coroner Andrew Walker conclude that the aircraft was not airworthy.
Five members of 2nd Battalion The Rifles were killed in two separate explosions in Helmand on July 10 2009.
The same year, another five servicemen - three from the Grenadier Guards and two from the Royal Military Police - died at the hands of a rogue Afghan policeman in the Nad-e'Ali district of Helmand Province on November 3.
Labour leader Ed Miliband said: "It is tragic news that six of our soldiers are missing, presumed dead, in Afghanistan. Our hearts go out to their families, friends and colleagues.
"This is a dark day.
"We salute all of our fallen and those who continue to serve in the face of the gravest danger. They are serving with bravery and courage and we owe them all a huge debt of gratitude."
Former Liberal Democrat leader Sir Menzies Campbell said: "This tragic incident serves only to remind us of the grave risks which we ask our young men and women in the armed forces to take every day on our behalf in some of the most dangerous places in the world.
"It isn't just the number of casualties which is so disturbing, it is the fact that the United Kingdom, along with other allies, has declared a date by which all combat forces will be withdrawn, and yet the efforts of the Taliban to destabilise Afghanistan and stand in the way of effective government continue unabated."
A total of 404 British service personnel have died, or are missing believed to be dead, since the start of operations more than a decade ago.
Former soldier Kris Hopkins, Conservative MP for Keighley and Ilkley in West Yorkshire, said: "I am absolutely devastated by this news.
"As a former member of the Duke of Wellington's Regiment, I was invited to have lunch with officers of 3rd Battalion the Yorkshire Regiment only two weeks ago in advance of their departure to Helmand.
"The loss of five men, together with a colleague from the Duke of Lancaster's Regiment, is a devastating blow to everyone out there.
"My sympathies go out to them all and, most importantly, the families of those brave soldiers who have lost their lives serving our country.
"Their sacrifice will never be forgotten."
At Battlesbury Barracks in Warminster, Wiltshire - the home of 3rd Battalion The Yorkshire Regiment - the dark green battalion flag emblazoned with a gold lion and white rose flew at half-mast.
A media pack gathered next to signs reading "Welcome to Battlesbury Barracks - Home of the Dukes".
Two uniformed soldiers re-lit a candle which had gone out next to the barracks' gates.
The candle was first lit when around 90 soldiers from the Corunna Company, of 3rd Battalion The Yorkshire Regiment, were deployed to Afghanistan less than a month ago.
The candle - which will remain lit until the last member of the battalion returns home - was the idea of the wives and partners of the soldiers, to act as a vigil for their loved ones.
Under the candle a text reads: "This flame serves to remind us of the commitment that the soldiers of this battalion are currently making on operations.
"It will be extinguished when the last soldier of the battalion returns safely to this base."