Boro Under-21s were beaten at the Riverside as Athletic Club emerged victorious.
Two goals in quick succession from Ekaine Azkune and Enaut Lete saw the visitors take control before Ander Izagirre headed home a third to round off a perfect half for the Spanish side.
The hosts extended their advantage moments into the second half through Asier Hierro which was enough to secure all three points.
Boro looked dangerous on the counterattack in the early stages of the game. A long kick from Shea Connor found George Gitau, but Oiet Gastesi claimed his cross well.
Moments later, Boro had more joy down the right when Gitau flashed a cross towards the back post, but Lennon could only find the side netting from a difficult angle.
After a quarter of an hour, Connor was called into action. Hierro found himself one-on-one with the Boro keeper, but the Boro keeper denied the striker superbly with his feet.
The visitors did find a way through just before the half-hour mark. Azkune cut inside onto his right foot and curled an effort into the far corner to give the Spanish side the early advantage.
Moments later, Bilbao found themselves celebrating again. Lete doubled their lead after rounding off a quick counter.
It got better for the visitors when Izagiree headed home from a corner kick for the visitor's third.
Just before the break, Ibon Sanchez whipped a free kick that looked destined for the top corner but a fingertip save from Connor denied the Bilbao skipper.
Middlesbrough U21: Connor, Gitau, Hunt, Woolston, McCormick, McCabe, Bailey Palmer (Coulson 75'), Finch (Patterson-Powell 75'), Cartwright (Stott 53'), Lennon (Nkrumah 58'), Matthews
Subs: Stott, Nkrumah, Lindo, Patterson-Powell, Coulson, Greenup, Lloyd
Athletic Club U21: Gastesi, Irurita (Osipov 71'), Izagirre, de Luis, Elías, Sola, Lete, Bujan (Adrián Pérez 45'), Sánchez (Elijah Gift 62'), Azkune (Sanz 45'), Hierro (Gerenabarrena 71')
Subs: Osipov, Gamen, Gerenabarrena, Nomayo, Elijah Gift, Adrián Pérez, Sanz
Straight from the break, the visitors had a fourth. After Fin Cartwright had a penalty appeal waved away the visitors darted up the other end before Hierro slotted it home.
Boro came close to pulling one back through Daniel Nkrumah. A mistake from the Bilbao keeper gave the winger a chance to fire one goalwards but his shot was deflected narrowly wide.
This was to be the last of the action at the Riverside with Athletic Bilbao taking all three points.
Mark Tinkler's side will be looking to bounce back when they face Blackburn Rovers in the Premier League 2 on Friday 17 January.
