Trailing 3-1 from the first leg, Tim Sherwood's side will be without a recognised centre-half, with Michael Dawson, Vlad Chiriches and Younes Kaboul all injured and Jan Vertonghen suspended.
Right-back Kyle Walker is also out, meaning Kyle Naughton and Danny Rose will likely start at full-back with Zeki Fryers at centre-half alongside a debutant at Estadio da Luz.
They will play in front of Brad Friedel because Hugo Lloris has not travelled with the squad.
In midfield, Erik Lamela is back in training but a long way from a first-team return, while Etienne Capoue, Paulinho and Mousa Dembele are also sidelined.
Emmanuel Adebayor has been left in England with a hamstring problem, so Roberto Soldado will start up front.