The flying Welshman has not recovered from a hamstring tear sustained on international duty in time to feature, while Wayne Rooney returns for the title-chasing visitors
Gareth Bale has been left out of the Tottenham squad to face Manchester United due to injury.
As revealed exclusively on Thursday, the Welshman sustained a hamstring tear on international duty in midweek and may also miss Spurs' FA Cup replay against Stevenage and the trip to face Everton next weekend.
Rafael van der Vaart also misses out, meaning Luka Modric appears likely to start on the left flank in Bale's absence, with Sandro and Jake Livermore in the heart of midfield.
For United, Wayne Rooney has recovered from the illness which ruled him out of England's 3-2 friendly defeat against the Netherlands in time to start, but Antonio Valencia remains absent.
Tottenham: Friedel; Walker, King, Kaboul, Assou-Ekotto; Lennon, Sandro, Livermore, Modric; Saha, Adebayor.
Subs: Dos Santos, Dawson, Kranjcar, Defoe, Rose, Nelsen, Cudicini
Manchester United: De Gea; Jones, Evans, Ferdinand, Evra; Young, Scholes, Carrick, Nani; Rooney, Welbeck.
Subs: Anderson, Giggs, Park, Hernandez, Fabio, Rafael, Amos.