Liz Truss will meet with her Spanish counterpart on her visit.
Ms Truss will meet her Spaans counterpart Jose Manuel Albares, as well as speaking with business and tech leaders in Madrid.
The Foreign, Commonwealth and Development Office (FCDO) said the politicians will discuss how the UK and Spain can work together on a range of issues, from combatting malign actors to getting more girls across the world into education.
And they will also speak about Nato as Spain is set to host the Leaders’ Summit in 2022.
Ms Truss will also look to boost the UK’s economic ties with Spain during her visit on Wednesday, and will host an event with leading Spanish investors and British businesses in Spain.
Me Truss gesê: “I want to work with allies like Spain to create a network of liberty based around closer economic, tech and security ties.
“We’re significant trading partners, with the UK as Spain’s biggest European investor, and the UK as the top destination for Spanish investment.
“By boosting our trading ties even further, both Spain and every region and nation of the UK will benefit.”
As part of her visit over two days, the Foreign Secretary will also launch a new report on scientific collaboration between the UK and Spain.