Swansea City host Valencia in one of the headline fixtures. The Spanish club are already assured of their place in the next round, but could be leapfrogged at the top of Group A by Michael Laudrup's men if the team from Wales take maximum points.
Swansea will be confident of doing so after the reverse fixture on matchday one ended in a surprise 3-0 win for the visitors, with Wilfried Bony, Michu and Jonathan de Guzman scoring the goals.
However, St Gallen and Kuban Krasnodar have not given up hope of progressing and the winner of their tie will be hoping for a Swansea defeat to keep their slim chances alive.
A draw between the third- and fourth-placed clubs would send Swansea through regardless.
Group I sees another clash between two sides who will be hopeful sealing their progression, with Lyon welcoming Real Betis to Stade de Gerland.
The La Liga outfit can qualify with a win, while both will go through if Lyon emerge victorious and Vitoria Guimaraes lose their clash with basement club Rijeka.
In Group F, Eintracht Frankfurt and Maccabi Tel Aviv face trips to Bordeaux and APOEL respectively, knowing wins would guarantee a place in the next stage.
There is a similar scenario in Group H, though Sevilla and Slovan Liberec will enjoy home advantage as they seek to ensure qualification against Freiburg and Estoril respectively.
Anzhi will look to put their dismal domestic campaign to one side as they go in search of a last-32 spot, and a point against Sheriff would be enough to see them through in Group K.
Tottenham have won all four of their matches so far and can guarantee top spot with a win against the already-eliminated Tromso of Norway.
Trabzonspor require just a draw at home to Apollon in Group J, while Lazio can also progress by defeating Legia Warsaw, who have yet to pick up a point in this year's competition.
In Group B, PSV Eindhoven must better the result of Chornomorets Odesa to make sure of their place in the knockout stages.
PSV travel to Ludogorets Razgrad, who have qualified, while Chornomorets are at home to already eliminated Dinamo Zagreb.
PAOK and AZ currently occupy the top two spaces in Group L, and require just a point apiece against Shakhter Karagandy and Maccabi Haifa respectively.
The winner of the clash between Genk and Dynamo Kiev will be guaranteed to emerge from Group G, while the loser of Rapid Vienna against Thun will be eliminated from the competition.
Wigan Athletic and Zulte Waregem meet at the DW Stadium and the former would qualify from Group D with a win should Maribor fail to defeat Rubin Kazan, who are through.
Qualification has already been resolved in Group C, where leaders Red Bull Salzburg head to Elfsborg with the chance to become the first club to win all six games in a Europa League group stage twice, and second-placed Esbjerg host Standard Liege.
The qualifiers from Group E have also been determined, though Fiorentina could seal first place if they extend their lead over Dnipro Dnipropetrovsk. The Italians take on Pacos de Ferreira in Portugal, while the Ukrainians welcome Pandurii Targu Jiu.
