The Bluebirds are in action for the first time since the plane carrying the Argentine disappeared over the Channel Islands a week ago. They visit Arsenal in what could have been Sala's debut for the club.
In the title race, City have been forced to play catch-up since cutting Liverpool's advantage at the top to four points by inflicting the Reds only league defeat of the season on January 3.
This week City can apply pressure by cutting the gap to a solitary point as they travel to struggling Newcastle 24 hours before Liverpool host Leicester.
AFP Sports picks out some of the main talking points ahead of the midweek games.
"He's going to be remembered as the best player we never had," one Cardiff fan said when asked how to put Sala's disappearance into words.
Signed from Nantes for a club record fee, struggling Cardiff hoped his goals could keep them in the Premier League. Now they must somehow try to achieve survival on the field while dealing with tragedy off it.
A minute's silence will be held before all Premier League games this week in honour of Sala and the plane's pilot David Ibbotson after the authorities called off their active search for the aircraft.
Once the action gets under way, though, Arsenal have to be ruthless in the fight for Champions League qualification -- victory would take them level on points with fourth-placed Chelsea, who visit Bournemouth on Wednesday.
Cup capitulation heaps pressure on Spurs
"In reality the most important thing is being consistently in the top four and playing in the Champions League," insisted Tottenham boss Mauricio Pochettino after crashing out of two cup competitions in four days.
Despite doing a remarkable job to turn Tottenham into top-four regulars, Pochettino is yet to win in a trophy in his five seasons at Spurs.
And by downplaying the importance of silverware, the Argentine has piled the pressure on his injury-ravaged side to hold onto their place in the top four to ensure Champions League qualification for a fourth straight season.
With Harry Kane and Dele Alli sidelined until March, a kind run of fixtures that sees Watford, Newcastle and Leicester visit Wembley before a trip to Burnley over the next month is just what Pochettino needs.
Solskjaer on cloud nine
United's caretaker boss Ole Gunnar Solskjaer acknowledged he is "loving" his role and can do no wrong, with a run of eight straight wins putting the Red Devils right back in top-four contention and into the last 16 of the FA Cup.
More of the same will be expected when Burnley visit Old Trafford on Tuesday fresh from being thrashed 5-0 on the other side of Manchester by City in the FA Cup at the weekend.
United's 3-1 win in the Cup at Arsenal on Friday was just as impressive and leaves Solskjaer spoiled for choice.
Alexis Sanchez scored and Romelu Lukaku provided two assists to make their case for a more regular start, but Solskjaer is expected to keep faith with in-form Marcus Rashford and Anthony Martial, who came off the bench to score at the Emirates.
Can Higuain hit the ground running?
Chelsea boss Maurizio Sarri finally has the striker he wanted in Gonzalo Higuain, and must now hope the Argentine's firepower keeps his side in the top four.
Higuain failed to find the net in Sunday's 3-0 Cup win over Sheffield Wednesday to get up to speed and will likely make his Premier League debut away to Bournemouth on Wednesday.
A 2-1 win over Spurs to reach the League Cup final last week suggests Sarri's side are a different prospect when Eden Hazard is restored to his favoured position on the left of a front three.
Higuain's presence should allow the Belgian to shine. The on-loan Juventus striker comes with a prolific record in club football.
Fixtures (kick-offs 1945 GMT unless stated)
Arsenal v Cardiff, Fulham v Brighton, Huddersfield v Everton, Wolves v West Ham, Manchester United v Burnley (2000), Newcastle v Manchester City (2000)
Bournemouth v Chelsea, Southampton v Crystal Palace, Liverpool v Leicester (2000), Tottenham v Watford (2000)