Pep Guardiola knows that any more slip-ups could prove fatal to their already faint title hopes, then, and Saturday's Manchester showdown begins a difficult run which sees City face United, Arsenal, Leicester City and Wolverhampton Wanderers over the festive period.
Here, Sports Mole looks at how they could line up for the derby.
Man City are able to welcome Ilkay Gundogan back into the squad for this match after he missed the Burnley win through suspension, but the German will have trouble regaining his place following the performance of the midfield trio at Turf Moor.
All of City's slightly lesser-used players will be on high alert as the fixtures begin to pile up, although Guardiola is more likely to rotate for next week's Champions League tie against Dinamo Zagreb than he is a borderline must-win Manchester derby.
Nonetheless, there could be changes with Benjamin Mendy pushing for a recall ahead of Angelino and John Stones potentially being preferred to Nicolas Otamendi due to the pace of United's attacking line.
Record goalscorer Sergio Aguero is still a week or so away from returning so Gabriel Jesus will likely lead the line fresh from his drought-ending double against Burnley.
Aymeric Laporte and Leroy Sane also remain sidelined with longer-term problems, but Oleksandr Zinchenko is in contention for the first time since undergoing knee surgery in October.