The Red Devils produced a rousing comeback from two goals down against Newcastle United before the international break, ending a four-match winless streak across all competitions.
However, they remain seven points off the pace already and will be underdogs for the journey to Chelsea, who are still unbeaten in the Premier League this season.
Here, Sports Mole looks at how an injury-hit United could line up against their fellow top-four hopefuls.
United could be without as many as seven first-team players this weekend, while Alexis Sanchez - the match-winner against Newcastle last time out - played the full 90 minutes for Chile on Wednesday night and returned late from the international break as a result.
Sanchez may once again be forced to settle for a place on the bench, then, with Mourinho likely to keep faith with Marcus Rashford following his impressive performance for England against Spain.
Juan Mata was a 19th-minute sub for United against Newcastle and helped to turn the game in their favour, which may earn him a start at his old employers ahead of Anthony Martial, with Jesse Lingard still injured.
Lukaku will also lead the line against his former club having rediscovered his scoring touch during the international break, but there could be changes in midfield with McTominay, Matic and Herrera all expected to miss the game.
United's turnaround against Newcastle came after Mourinho switched to a back three of Matic, Paul Pogba and Chris Smalling, and he could look to experiment again this weekend, although he is expected to match up against Chelsea's 4-3-3 system.
Fellaini is the most likely of the doubtful players to recover in time, while Fred could also come into midfield for his first league start in almost a month.
Matic and Shaw both withdrew from their respective international squads due to injury and face a race against time to prove their fitness, while captain Antonio Valencia is also in the running to return to the side.
Much will be made of the centre-back partnership too; Eric Bailly was hooked after just 19 minutes against Newcastle and Victor Lindelof was left on the bench throughout, despite Mourinho reverting to two unrecognised centre-backs instead.