La Rojita advanced to this stage of the competition as Group B winners, picking up seven points from their three matches, while Mladi Vatreni claimed second in Group D to progress to the knockout round.
Spain, as mentioned, topped Group B to advance to the quarter-finals, beating Slovenia and Czech Republic, in addition to drawing with Italy during a solid group stage.
Incredibly, La Rojita have never lost an Under-21 European knockout match before the final since the tournament format was introduced in 1998, and there is no question that they will be the favourites to advance to the semi-finals, where either Portugal or Italy will be waiting on June 3.
Spain have won five European Under-21 Championship titles, which is the joint-most in the history of the competition alongside Italy, and they are the holders, having triumphed in 2019.
The fact that Spain have lost just three of 39 European Under-21 Championship matches is an indication of the size of the task for Croatia, while they have not been beaten in a last-eight tie since 1990.
Croatia, meanwhile, are in the tournament's knockout round for the first time, managing to finish second in Group D behind runaway leaders Portugal.
England actually finished bottom of the section, with Croatia incredibly qualifying despite losing two of their three matches, including a 2-1 reverse to Aidy Boothroyd's side in their last game at the end of March.
Domagoj Bradaric's late stunner saw Croatia advance to the final eight, with England failing to win by the two-goal margin that was required to progress on goal difference.
Igor Biscan's side will undoubtedly be the underdogs against Spain, but they were victorious in the last meeting between the two nations at this level, running out 3-0 winners during qualification for the 2017 finals.
All three of Croatia's previous Under-21 European final appearances ended in the group stage, and this is almost a free hit for Mladi Vatreni, who certainly have players capable of causing De la Fuente's side issues.
As for Croatia, Bradaric, Luka Ivanusec and Josko Gvardiol have been named in Zlatko Dalic's senior Euro 2020 squad, but all three players have been given permission to play in this match before leaving ahead of a potential semi-final.
Spain Under-21s possible starting lineup:
Fernandez; Guillamon, Mingueza, Miranda, Cuenca; Beltran, Cucurella, Zubimendi; Ruiz, Diaz, Gil
Croatia Under-21s possible starting lineup:
Semper; Bradaric, Sverko, Franjic, Sutalo; Moro, Ivanusec, Majer, Durasek; Kulenovic, Musa
We say: Spain Under-21s 2-0 Croatia Under-21s
Croatia, as mentioned, have the players to hurt Spain, but we are finding it difficult to back a surprise result here. La Rojita have so much talent across the field, and we are fully expecting the five-time champions to march their way into the semi-finals of the competition.
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