There had been speculation on social media that Haaland would not travel with the matchday squad due to a foot injury, and the Premier League's top scorer has indeed not made the trip to Luton, with Pep Guardiola stating in a pre-match interview with Sky Sports that he has a "bone stress reaction" in his foot.
Doku is also absent after failing to shake off an unspecified leg issue that forced the winger to miss Wednesday's 1-0 defeat at Aston Villa.
Guardiola has made a total of four changes to his first XI from that loss at Villa Park, with Haaland, Rico Lewis, John Stones and Manuel Akanji all making way for Rodri, Jack Grealish, Nathan Ake and Mateo Kovacic.
Both Rodri and Grealish return to the starting lineup after missing the midweek defeat to Villa through suspension, and the duo are set to start in centre-midfield and on the left wing respectively.
Ake will line up alongside captain Kyle Walker, Ruben Dias and Josko Gvardiol in the back four, with Kovacic operating in the engine room next to Rodri.
Grealish, Phil Foden and Bernardo Silva will all operate in the final third alongside Julian Alvarez, who is set to take up the centre-forward role in the absence of Haaland.
As for Luton, Rob Edwards has made three changes to the side that lost 4-3 at home against Arsenal on Tuesday, with captain Tom Lockyer, Marvelous Nakamba and Ryan Giles all returning to the first XI.
Man City loanee Issa Kabore is ineligible to face his parent club, so Alfie Doughty will switch over to right wing-back to allow Giles to operate on his favoured left flank.
Lockyer is recalled at the heart of the defence to play alongside former Manchester United man Teden Mengi and Amari'i Bell, with Gabriel Osho not involved in the matchday squad.
Nakamba replaced Pelly Ruddock Mpanzu and will link arms with Ross Barkley in centre-midfield, while a front three of Andros Townsend, Elijah Adebayo and Jacob Brown remains intact, meaning Carlton Morris is forced to begin on the substitutes' bench once again.
Luton Town: Kaminski; Mengi, Lockyer, Bell; Doughty, Nakamba, Barkley, Giles; Townsend, Adebayo, Brown
Subs: Krul, Andersen, Berry, Morris, Chong, Mpanzu, Clark, Lokonga, Johnson
Manchester City: Ederson; Walker, Dias, Ake, Gvardiol; Rodri, Kovacic; Bernardo, Foden, Grealish; Alvarez
Subs: Ortega, Carson, Phillips, Stones, Gomez, Akanji, Nunes, Bobb, Lewis