Centre-back Cahill has been struck down by a virus ahead of the trip to the Riverside, while right-back Azpilicueta is sidelined with a leg problem.
Interim manager Rafael Benitez plans to rotate his squad in a bid to deal with the busy fixture list, meaning captain John Terry may be rested. Long-term absentee Oriol Romeu continues to miss out with a knee injury.
Middlesbrough boss Tony Mowbray will be without Josh McEachran, Kieron Dyer and Sammy Ameobi who are ineligible.
Midfielder McEachran has not played in the competition to date under the terms of his loan agreement with Chelsea, while Dyer and Ameobi are cup-tied.
Mowbray will also be without striker Lukas Jutkiewicz (ankle) and central defender Jonathan Woodgate (calf), although the latter has a chance of returning for the league clash with league leaders Cardiff at the weekend.
In addition, Stuart Parnaby (hamstring tear), Justin Hoyte (hip) and Julio Arca (toe) remain on the sidelines.
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