Pep Guardiola and Ruben Amorim will both be forced to be bold with their team selections for the Manchester derby this weekend.
Man City host local rivals United for the first derby of the season with both clubs in desperate need of a morale-boosting victory.
Amorim masterminded a 4-1 win over Guardiola with Sporting last month
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Amorim masterminded a 4-1 win over Guardiola with Sporting last monthCredit: Getty
Premier League champions City thought they'd turned a corner in their sliding form after a 3-0 win over Nottingham Forest last week.
However, Guardiola's men lost further ground in the race to defend their crown on Saturday following a 2-2 draw at Crystal Palace.
The club are eight points behind leaders Liverpool, who also have a game in hand, and could slip out of the top four with another defeat.
Their Manchester neighbours are in even more dire straits following a quick end to the new manager bounce under Amorim.
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An emphatic win over Everton was followed up with two losses to Arsenal and Forest within a week to leave United in 13th.
Amorim will be buoyed by his impressive Champions League victory over Guardiola's City with former club Sporting Lisbon last month.
Man City
Guardiola's defensive crisis deepened after Rico Lewis received a controversial red card at Selhurst Park.
After equalising for City against Palace, the 20-year-old was sent off after being booked twice - first for dissent, and then for a foul.
Replays later showed Lewis was wrongly penalised for his challenge on Trevor Chalobah but his ban can't be overturned as it was the result of two yellow cards, not a straight red.
His one-match domestic suspension means Josko Gvardiol will be needed to return to the left after a short stint at centre-back.
Lewis has featured in 14 of Man City's 15 Premier League matches this season
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Lewis has featured in 14 of Man City's 15 Premier League matches this seasonCredit: Getty
Haaland questioned Walker after City conceded their first goal against Palace
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Haaland questioned Walker after City conceded their first goal against PalaceCredit: Getty
Guardiola will be hoping one of the three absentees he has in that position can partner Ruben Dias at the heart of his defence.
Manuel Akanj seems the most likely, with Nathan Ake and John Stones both struggling with more severe fitness issues this term.
In goal, Stefan Ortega has played three consecutive Premier League matches but Guardiola has insisted Ederson remains his No.1 choice.
The Brazilian's trademark vision and ability to play out from the back may make this the perfect game to reclaim his starting berth.
Ederson registered his fourth Premier League assist earlier this season - one more than Antony - and would back himself to increase that tally by exploiting the space behind Man United's fullbacks.
In midfield, Bernardo Silva and Ilkay Gundogan would be the safe pairing with Mateo Kovacic and Rodri still in the treatment room.
Ederson dropped out of the City side after a series of high-profile errors
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Ederson dropped out of the City side after a series of high-profile errorsCredit: AFP
However, Jack Grealish and Jeremy Doku could both return to the starting XI after being rested away at Palace.
Grealish will be desperate to build upon his new central position where he was deployed in the 3-0 win over Nottingham Forest.
The England international had almost exclusively operated from the left wing under Guardiola before the change in tactics last week helped inspire City to their only win in their past nine games.
Grealish's assuredness in possession and ability to drive City up the pitch would alleviate issues Gundogan could face with United's press.
Grealish also played centrally under England interim manager Lee Carsley
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Grealish also played centrally under England interim manager Lee Carsley
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The inclusion of the former Aston Villa captain will negate the need for Matheus Nunes, with Doku's speed a more vital asset to attack.
The Belgian registered a goal and assist against Forest before being rested against Palace and will hope to reclaim his spot on the left.
Doku's international captain Kevin De Bruyne is a no-brainer to play in the No.10 role behind Erling Haaland if fit.
Guardiola's final selection headache will come on the right, with Silva set to play either in this position or in a deeper midfield role.
The Portugueses' defensive qualities may be needed in transition to counter United's fast breaks as opposed to what Phil Foden offers.
The latter has struggled for fitness and form this season and has missed the past two matches because of bronchitis.
Grealish has been waiting years to play centrally for City
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Grealish has been waiting years to play centrally for City
Manchester United
Amorim has had precious little time to learn about his new players as he works on implementing his favoured 3-4-3 system.
Andre Onana's position between the sticks remains nailed on despite the Cameroonian's major mishap in the loss to Forest on Saturday.
Matthijs de Ligt has been Amorim's preferred pick as the central defender in his back three, with Lisando Martinez on the left.
Leny Yoro endured a baptism of fire on his first Premier League start and Noussair Mazraoui will likely be needed on the opposite flank.
Diogo Dalot and Amad Diallo are Amorim's settled options at wingback, with Kobbie Mainoo and Manuel Ugarte in midfield.
A decision will be needed over the two attacking no.10s, with Alejandro Garnacho in hot water following the Forest defeat.
Diallo has been a rare bright spark in the emerging Amorim era
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Diallo has been a rare bright spark in the emerging Amorim era
The Argentine has been a regular under Amorim but more social media antics put him under fire - this time at the expense of international teammate Martinez.
Garnacho has preferred to operate in pockets of space rather than hold the width, which is what will be needed against a struggling Kyle Walker.
Marcus Rashford notched the first goal of the Amorim era after 81 seconds against Ipswich while playing as the number nine.
He reverted to his more orthodox left-wing role and scored a brace against Everton but has since been relegated to the bench.
Garnacho was taken off in the 59th minute and now Rashford may get his chance
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Garnacho was taken off in the 59th minute and now Rashford may get his chanceCredit: Getty
Rashford has netted two goals in his past four Premier League meetings with City, including a stunner in this fixture in March.
The 27-year-old will relish the chance to isolate England teammate Walker, who was lambasted by Haaland for another error on Saturday.
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United captain Bruno Fernandes will take up the other attacking midfield position with Rasmus Hojlund hoping to lead the line.
The Danish striker scored the Red Devils' opener against Forest and offers a more physical presence to hold up play and run in behind than Joshua Zirkzee.
Rashford will be under pressure to deliver
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Rashford will be under pressure to deliver