Cape Town - North London rivals Arsenal and Tottenham Hotspur will both have the chance to pile the pressure on Pep Guardiola by leapfrogging his Manchester City side at the top of the Premier League table on Saturday.
The Gunners, level on points with City, are at home to struggling Middlesbrough while Spurs, a point behind, travel to Bournemouth.
City, still smarting from Wednesday's 4-0 Champions League loss away to manager Guardiola's former club Barcelona, are not in action again until Sunday when they face Southampton at Eastlands.
Should Arsenal and Tottenham both slip up, City could still yield top spot to Liverpool if the Merseysiders, currently two points off the summit following their goalless draw with Manchester United, beat West Bromwich Albion at Anfield on Saturday.
Arsenal thrashed Ludogorets 6-0 in the Champions League in midweek, with Mesut Ozil scoring a hat-trick against the Bulgarians at the Emirates.
The Gunners are now unbeaten in 11 matches and veteran manager Arsene Wenger said: "I feel that at the moment, because we win game after game, our confidence is high."
Middlesbrough, by contrast, are without a win in their last six league matches and are only above the relegation zone on goal difference.
Tottenham face a potentially tricky trip to south coast side Bournemouth, who've won plaudits for the quality of their football under young English manager Eddie Howe.
"The job he has done is unbelievable," said Spurs boss Mauricio Pochettino. "They show every week that they're a team with principles."
Guardiola is also known for the courage of his football convictions and he insisted those would not change after he saw Lionel Messi, once his star player, score a hat-trick against City on Wednesday.
To make matters worse, City goalkeeper Claudio Bravo, himself a former Barca player, was sent off for saving Luis Suarez's effort when outside his area after gifting the ball to the Uruguayan striker as he tried to follow Guardiola's call to play out from the back.
Guardiola won his first 10 games as City manager but the club have now gone four games without a victory, a 3-3 draw at Celtic followed by a 2-0 defeat at Tottenham before they squandered two penalties in a 1-1 draw against Everton last Saturday.
"Starting in Glasgow, own goals in White Hart Lane (against Tottenham), missing penalties, we give a lot for the opponents," Guardiola said.
Southampton, by contrast, were unlucky to lose 1-0 to Inter Milan in the Europa League on Thursday after manager Claude Puel made several changes to the side that beat Burnley 3-1.
Manchester United manager Jose Mourinho returns to former club Chelsea on Sunday, fresh from guiding the Red Devils to a 4-1 Europa League win over Fenerbahce – a match in which world record signing Paul Pogba scored twice and veteran striker Wayne Rooney started after three successive club games as a substitute.
Chelsea will look to carry on from their 3-0 win over faltering Premier League champions Leicester.
Despite their domestic problems, Leicester maintained their perfect record in the Champions League with a 1-0 win over Copenhagen on Tuesday.
Foxes manager Claudio Ranieri, whose side next play Crystal Palace, explained the difference in form by saying: "You spend a lot of energy, mental energy, in the Champions League. When you come back a little more down, it's normal."
Bottom-of-the-table Sunderland go in search of their first league win this season at West Ham on Saturday, with fellow strugglers Swansea at home to Watford.
Stoke travel to Hull and Burnley are at home to Everton.
SATURDAY, OCTOBER 22
Bournemouth v Tottenham Hotspur - 14:30
Arsenal v Middlesbrough - 16:00
Burnley v Everton - 16:00
Hull City v Stoke City - 16:00
Leicester City v Crystal Palace - 16:00
Swansea City v Watford - 16:00
West Ham United v Sunderland - 16:00
Liverpool v West Bromwich Albion - 18:30
SUNDAY, OCTOBER 23
Manchester City v Southampton - 14:30
Chelsea v Manchester United - 17:00