Michael Laudrup's men booked their place in the competition by winning the Capital One Cup last season and they have negotiated qualifying ties against Malmo and Petrolul Ploiesti.
Swansea now have the opportunity to travel to Spain and play at the 55,000-capacity Mestalla in the sort of fixture that would have seemed like a distant dream to fans just a few seasons ago.
Laudrup has confidently claimed that his side can 'beat anyone' in the Europe League, and they will be looking to make a strong start in their bid to advance from a group that also contains Swiss side St Gallen and Kuban Krasnodar of Russia.
Swansea go into the match on the back of a 2-2 draw with Liverpool which left them with four points from their opening four Premier League games of the season.
Winger Pablo Hernandez has been ruled out of the clash with his former club due to a hamstring injury.
Leon Britton is banned having been sent off against Petrolul Ploiesti in the play-off round, while a thigh injury is set to keep defender Neil Taylor sidelined.
But record signing Wilfried Bony has made the journey to Spain despite picking up a rib injury against Liverpool on Monday, and the striker will be assessed following training.
Valencia have endured a tough start to the Primera Liga season and are currently 16th in their domestic table after losing three of their first four games.
Pablo Hernandez will miss out on the chance to face his former Valencia team-mates as a hamstring strain keeps the winger out of Swansea's Europa League clash at the Mestalla.
Midfielder Leon Britton is another absentee, having been sent off against Petrolul Ploiesti in the play-off round, while a thigh injury is set to keep defender Neil Taylor sidelined.
But record signing Wilfried Bony has made the journey to Spain despite picking up a rib injury against Liverpool on Monday, and the striker will be assessed following training.
Provisional squad: Vorm, Amat, Flores, Williams, Shelvey, Michu, Bony, Dyer, Lamah, Routledge, Monk, De Guzman, Canas, Rangel, Pozuelo, Tremmel, Davies, Tiendalli, Vazquez.
