A controversial offside decision means Swansea's quest to secure a place in the knockout stages of the Europa League will go down to the wire after defeat to Valencia at the Liberty Stadium.
A draw would have been enough to take Swansea through from Group A with a game to spare, but they fell behind to Daniel Parejo's 20th-minute strike and then lost striker Wilfried Bony to a worrying hamstring injury.
They thought Alvaro Vazquez had levelled just before the break when Diego Alves could not hold Jonjo Shelvey's shot and the Spaniard tapped in, but the flag went up despite replays suggesting the two Swansea players were onside.
If the goal had stood, it would have been enough to seal a spot in the last 32, but instead Swansea must wait until their final game against St Gallen to discover their fate.
Michael Laudrup's side are three points clear of third-placed Kuban Krasnodar, with the Russians having to go to group winners Los Che in the final round and Swansea three goals better off.
Valencia were much improved from the first meeting between these two sides and deserved their lead.
Gerhard Tremmel did not deal with a Sergio Canales corner and Parejo slotted home when Juan Bernat's deflected shot fell to him.
Parejo went close to a second and forced Tremmel into sprawling save before Swansea saw Bony head off pulling up chasing a long ball.
The key moment soon arrived as Bony's replacement Vazquez finished from close range after Shelvey could not find the net, but the flag went up to Swansea's fury.
And the Welsh club's night was summed up when Jeremy Mathieu cleared a goalbound effort off the line and Angel Rangel limped off in the dying minutes.
Swansea had enjoyed a famous 3-0 win when the sides met at the Mestalla in the opening round of Group A fixtures, but there quickly appeared little chance of a repeat as Valencia started with an authority and crispness in their passing.
However, it was the hosts who had the first real chance. Alves punched an Alejandro Pozuelo corner straight at Bony, who headed it back just wide of the left-hand post.
Nathan Dyer also threatened aerially from a Neil Taylor cross, only for the visitors to strike the first blow.
Tremmel's punch fell to Bernat, and when his shot struck Roland Lamah it fell perfectly for Parejo to slot home.
Swansea responded with an extended spell of pressure, but failed to work Alves with Tremmel the busier keeper.
The German had to tip a low Parejo shot away as it headed for the bottom corner, while Jonas worried him with a fizzing drive from distance.
Swansea's cause was not helped by the sight of record signing Bony being helped off; with Michu also currently sidelined, the Ivorian's injury comes at a particularly bad time.
The hosts were left furious as Vazquez's effort was ruled out moments later and they surrounded the assistant referee before being ushered away by Italian referee Luca Banti.
The decision looked to be wrong and the ill-feeling spilled over as Chico Flores and Joao Pereira had to be kept apart as the teams headed off at the break after a clash just before the whistle.
Valencia almost made the most of the let-off when Canales produced a lovely pass to split the home defence, only for Sofiane Feghouli to fire across the face of goal.
Swansea thought their casualty list was set to extend when Jordi Amat went down after a clash of heads.
The defender was fine to continue, but only after a shambolic episode as Swansea failed to locate a spare shirt in a similar manner to an incident involving Michu against St Gallen earlier in the campaign.
Swansea pressed for the goal that would put them through and substitute Jonathan de Guzman forced a save from Alves, who also kept out Vazquez's follow-up and a misdirected Pozuelo effort.
Vazquez was then denied again as Mathieu superbly blocked on the line after the striker had beaten Alves to compund Swansea's frustrations.