Porto currently top Group H having collected four points from their first two games, but it has been a different story for Bilbao, who are bottom on one point.
Bilbao had the better of their meeting 58 years ago, however, with the Spanish side triumphing in their two-legged affair in the 1956-57 European Champion Clubs' Cup preliminary round.
Porto's home record against Spanish opposition is fairly mixed, with nine wins, three draws and eight defeats from 20 matches. However, Bilbao have won just one of their four matches in Portugal, losing twice in the process.
Porto will enter the match off the back of a 3-1 defeat to Sporting Lisbon in the third round of their domestic cup at the weekend. That said, they are second in the Primeira Liga, four points behind leaders Benfica after seven matches and have lost just one of their 11 matches this season.
Bilbao, however, who finished fourth in La Liga last season, have made their worst ever start to a Spanish league season, collecting just five points from eight games.
They started their Group H campaign with a goalless draw at home to Shakhtar Donetsk, but lost 2-1 at BATE Borisov last time out. The Spanish side are also without a win in eight games and have failed to score in half of their 12 matches in all competitions this season.
Porto have no fresh injury concerns, but they will be without the services of Goncalo Paciencia, who has a knee problem. There are not expected to be too many surprises in their XI, with Jackson Martinez leading the line.
Possible starting lineups
Porto: Fabiano; Danilo, Maicon, Martins Indi, Sandro; Brahimi, Herrera, Marcano; Torres, Martinez, Tello
Bilbao: Iraizoz; Iraola, Gurpegi, Laporte, Balenziaga; Rico, Iturraspe, Benat; Muniain, Aduriz, De Marcos
Sports Mole says: 2-0