With Marek Suchy banned and a host of first-team players - including captain Marco Streller - struggling for fitness, the Swiss champions face a tough test against the Spaniards
The Swiss champions were punished by Uefa last week after the behaviour of their fans caused the second leg of a 2-1 aggregate victory over Salzburg in the last round to be suspended for 13 minutes.
As a result, the Valencia game will be played behind closed doors.
The ruling will no doubt have come as a significant blow to Basel, who are looking to better their 2012-13 performance in this competition when they lost out to eventual champions Chelsea in the semi-finals.
Basel's run of three European matches without conceding on home soil could prove daunting for Juan Antonio Pizzi's visitors, but the Spanish outfit have won all five of their Europa League away matches this season, so there is a real sense that something has got to give.
Valencia have also kept clean sheets in their last four matches at home and away in the competition - one more would give them a tournament record.
The clubs have not met in continental competition since the 2002-03 Champions League group stages, when Valencia claimed a 6-2 victory at home, before battling to a 2-2 draw on the road.
Current Basel coach Murat Yakin played in both of those fixtures, but will have to contend with the threat of Pablo Alcacer this time round - the joint-top goalscorer still involved in the competition.
In addition to a lack of personnel in the stands, Basel also face something of a crisis on the pitch, with defenders Arlind Ajeti, Kay Voser and Behrang Safari (all thigh) doubtful, while Ivan Ivanov (knee), Marco Streller (groin) and Endogan Adili (knee) are all set to miss out.
Marek Suchy and Giovanni Sio are both suspended.
Valencia have similar concerns at the back, with Diego Alves (hamstring), Victor Ruiz (thigh), Ricardo Costa (ankle) and Philippe Senderos (hamstring) all carrying injuries, and midfielder Javier Fuego serving a suspension.