The ECB's vice president position is currently held by Portugal's Vitor Constancio who's eight-year term ends May 31.
The search for a number two at the central bank kicks off two years of personnel changes within the ECB's executive board, which consists of four board members, the vice president and president.
De Guindos, 58, has been Spain's economy minister since the conservative People's Party (PP), headed by Prime Minister Mariano Rajoy, won the 2011 election and has helped steer the country though its worst economic crisis in decades.
Before taking the helm at the Economy Ministry, de Guindos worked as a head of the financial sector in PricewaterhouseCooper in Madrid and as head of Nomura Securities and Lehman Brothers in the Iberian peninsular before that.
Euro zone finance ministers will vote on Feb. 19 for the ECB candidate, ahead of a European Parliament hearing and final appointment by EU leaders.