The pair's absence was confirmed as the teams were announced for the fixture at the Tottenham Hotspur stadium.
Rodrigo is believed to be out with a minor foot injury while Raphinha is thought to be suffering from an illness.
Rodrigo featured for Spain in their 1-0 victory over Sweden last Sunday after coming on as a second-half substitute.
Raphinha was most recently in action for Brazil against Argentina in a World Cup qualifier late on Tuesday night.
With both forwards out, Joe Gelhardt has been deployed in a lone striking role. Leeds have had a number of injury problems this season with Patrick Bamford and Luke Ayling already ruled out ahead of the trip to the capital.
Tottenham Hotspur: Lloris, Tanganga, Dier, Davies, Royal, Hojbjerg, Winks, Reguilon, Moura, Son, Kane. Subs: Rodon, Gil, Gollini, Sanchez, Bergwijn, Alli, Ndombele, Doherty, Sessegnon.
Leeds United: Meslier, Dallas, Llorente, Cooper, Struijk, Phillips, Forshaw, James, Harrison, Klich, Gelhardt. Subs: Klaesson, Firpo, Drameh, Cresswell, McCarron, McKinstry, Jenkins, Greenwood, Roberts.