European officials have estimated that Greece's financing needs could require an aid package of "30 billion, 40 billion, 50 billion euros", the minister told reporters in the northern city of Pamplona according to his press office.
Without confirming that talks were under way for a third bailout, the minister said Spain would contribute "around 13 percent of the amount" if another aid package were to be granted to Greece.
German newspaper Rheinische Post reported on February 25, citing sources in Berlin, that a third bailout for Greece would be worth €20 billion.
It is "way too early" to talk of a third bailout, a spokesman for Germany's finance ministry said at the time.
A third bailout would be a serious reversal for Greece's new hard-left government which swept to power in January on the promise that Athens would leave the era of European Union bailouts and their associated spending cuts behind.
Greece would prefer to receive a credit line but "it is more likely that we will move towards a new programme", a senior European official said on Tuesday.
Greece received two bailouts, in 2010 and 2012, worth a total of €240 billion and new Greek Prime Minister Alexis Tsipras has repeatedly said there would be no "third memorandum" as the previous agreements are known.
De Guindos' comments come after a weekend of tense exchanges between Athens and Madrid.
Tsipras said on Saturday that during recent talks that earned Greece a four-month extension to its bailout, pressure from certain other European countries "had the character of blackmail" - pointing especially to Spain and Portugal.
"Conservative forces (in Europe) tried to set a trap for us, to drive us into financial asphyxia," he added.
Spanish Prime Minister Mariano Rajoy hit back on Sunday, accusing Tsipras of seeking an "external enemy" and of "not being serious".
Both Madrid and Lisbon have filed official protests against Tsipras's comments with Brussels.
"Neither Spain nor Portugal were the hardest nations" at the talks, de Guindos said on Monday.