Hugo Lloris had a day to forget in North London and should pass the gloves over to Pierluigi Gollini for the time being, while Cristian Romero and Joe Rodon will hope to partner up in front of the Italian.
Ben Davies is a shoo-in to come in for Sergio Reguilon, while Japhet Tanganga - who was hauled off at half time in the North London derby - may hold his place as Santo keeps Emerson Royal fresh for the Newcastle United clash.
Harry Winks was left out of the squad entirely at the weekend, but the Englishman - along with Giovani Lo Celso and Oliver Skipp - could return to the engine room as Tanguy Ndombele, Dele Alli and Pierre-Emile Hojbjerg make way.
With no Bergwijn or Sessegnon ready to deputise, Lucas ought to keep his spot in attack after Jack Clarke was not involved against Rennes, while Son Heung-min should drop out for Bryan Gil on the left.
Dane Scarlett made the bench at the Emirates as Harry Kane failed to fire and made two mistakes for Arsenal's third goal on the day, but the England captain will hope to claim a couple of confidence-boosting goals here.
Tottenham possible starting lineup: Gollini; Tanganga, Romero, Rodon, Davies; Lo Celso, Skipp, Winks; Lucas, Kane, Gil