In a reception in the City of London business district before holding talks with Prime Minister Theresa May, the monarch also said there was a need to "minimise future obstacles.
"We cannot deny that the scenario created by Britain's decision to leave the EU has created uncertainty and doubts for our major companies, and especially for our small and medium enterprises," King Felipe said.
"We must ensure that the negotiations reduce such uncertainty to the minimum. It is vital that the framework of our future relations create the conditions for a closer trading relationship by trying to minimise future obstacles," the monarch said.
British exports to Spain were worth 16.7 billion euros (USD 19.1 billion) in 2015, while Spanish imports were worth 28 billion euros.
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Spanish investments in Britain topped 82 billion euros that year. Meanwhile Britain is the second-biggest investor in Spain, representing 12 percent of total foreign investment.
"These investments created around 110,000 jobs in Spain, where around 1,000 British companies have a base," the king said.
The main Spanish companies in Britain attended the reception, including the banks Santander and Sabadell, Inditex (Zara) and Ferrovial, which was involved in building London's new Underground train line.
"We are confident that the agreement on Britain leaving the European Union... Will soon give you the necessary certainty to continue living your lives in peace and with confidence," the sovereign said.
There are around 300,000 Britons living in Spain, many of whom are retired and depend on free medical care under EU rules. The 116,000-odd Spaniards in Britain are mainly workers.
"We know that many of you wish to remain in Britain after it leaves the EU, carrying on with your work and way of life, which began when there were no shadows of uncertainty about the future," the king said.
Before the reception at the embassy, King Felipe and Queen Letizia visited Westminster Abbey in London, where they laid a wreath at the tomb of the unknown soldier and saw the tomb of Eleanor of Castile, the Spanish wife of England's king Edward I, who died in 1290.