Aymeric Laporte looks set to be out for the rest of 2019 after undergoing knee surgery, dealing a significant blow to Manchester City.
The 25-year-old was sent to Barcelona to see trusted specialist Dr Ramon Cugat and, following tests, the surgeon operated on the defender’s cartilage and meniscus damage.
Laporte has at least not ruptured his anterior cruciate ligament, which was first feared when he fell to the ground in agony after a clumsy challenge on Brighton's Adam Webster in the 4-0 victory on Saturday.
But an absence of at least three months will have a sizeable impact on Pep Guardiola's squad as City bid to become the first side to win three successive Premier League titles since 2009.
Guardiola had described Laporte as "the best left-sided centre-back in Europe" ahead of the Brighton game.
Indeed, such is the esteem that the Frenchman is held in, Laporte is the only transfer target that Guardiola has ever returned to after initially being turned down.
City first tried to sign him in the summer of 2016 before he finally joined from Athletic for a fee of £57 million (€65m/$74m) in January 2018.
Since then he has played in every Champions League match - other than a trip to Basel shortly after arriving - and has made more Premier League starts for the club than any other outfield player.
He will, thus, not be easy to replace.
Frustratingly for Guardiola, his squad was already one man short of the four centre-backs he would have preferred to have right now.
Vincent Kompany left at the end of last season after 10 years with the club to take over as player-manager at Anderlecht. The veteran wasn't replaced, leaving City with just two other senior centre-backs in Nicolas Otamendi and John Stones – the latter will return from his own injury after the international break.
Pep does have some exciting youngsters emerging from the Academy in Eric Garcia and Taylor Harwood-Bellis. Highly-rated Spain Under-19 international Garcia impressed in three appearances in last season's Carabao Cup, while Harwood-Bellis stood out on the pre-season tour to the Far East.
One or both could feature in the Carabao Cup clash at Preston later this month but Guardiola will want more experience in the Premier League.
City had looked at signing a fourth centre-back in the summer but opted not to meet Leicester's asking price for England defender Harry Maguire, who moved to United for £80m (€88m/$97m) instead. They also decided against bidding for Dutchman Matthijs de Ligt - the client of agent Mino Raiola – who transferred to Juventus.
Midfielder Fernandinho was identified as City's fourth-choice option with Guardiola spotting his potential to play in that position.
The Catalan has said that the Brazilian could play in 10 different positions and he became a viable centre-back alternative after deputising in the role in the 3-1 victory over Arsenal last season.
Following the club-record signing of Rodri from Atletico Madrid in the summer, City now have two recognised holding midfielders and Fernandinho is able to be used as cover for both positions.
But replacing Laporte will not be easy.
Defensively he has been consistently outstanding, the one exception being two bad mistakes in last season's Champions League defeat to Tottenham.
So uncharacteristic were his errors that Guardiola put them in the same category as Sergio Aguero's tight offside call - spotted by VAR - and Fernando Llorente's “handball" winner when describing City's lack of fortune on that night.
But it's not only his defensive qualities that make him a key figure in Guardiola's setup.
Laporte is crucial to City's attacking style, particularly against sides that defend with a low block.
Only Liverpool's Virgil van Dijk made more passes out of defence last season - and he was named UEFA Men’s Player of the Year last week.
Laporte shifts possession quickly, driving balls out to the right wing to change the emphasis of the attack or firing balls into David Silva and Kevin De Bruyne in between the lines in order to build up momentum.
While opponents will still find it difficult to create opportunities against a side that will continue to dominate possession, his passing ability could be difficult to replace.
Fernandinho is a more natural and dynamic passer – although he lacks Laporte’s aerial quality - and when Ilkay Gundogan played just ahead of him in that win against the Gunners, City dominated the game with speedy and intelligent passing.
Otamendi, who could have left in the summer had Kompany not departed first, will become an even more key figure.
He actually holds the Premier League record for most passes in a season as a defender - 3,074 in City's ‘Centurion’ campaign.
But some opponents have tried to isolate him on the ball, as his occasionally slow passing is seen as a perceived weakness.
Stones, meanwhile, has built a reputation for his ball-playing skills. But he too can be prone to lapses, such as his mistake for England that cost them in the Nations League defeat to the Netherlands in the summer.
Guardiola has been full of praise for the former Everton defender but for the past two seasons, Stones has been out of the picture for the crucial second half of the campaign.
While City are reluctant to put a timescale on the length of Laporte's absence, they hope to have him back for the run-in this term.
Coping without him until then will not be straightforward for Guardiola.