Ayyoub Bouaddi was given a start by Enzo Maresca against Brighton on Saturday.
City suffered a second straight Premier League defeat as Yasin Ayari struck in the 11th minute from a quick free-kick taken by Lewis Dunk, handing Brighton their first away win over the Blues at the 18th attempt.
The result came three days after the Blues beat Fabian Hürzeler's side 4-3 on penalties in the Carabao Cup, and it ended a run of 24 consecutive Premier League games in which Manchester City had found the net.
Maresca named Ayyoub Bouaddi, Enzo Fernandez and Elliot Anderson together in midfield, a week after he explained the decision to leave the 19-year-old on the bench for the 2-1 defeat at Aston Villa .
Speaking in his post-match press conference, Maresca was asked about his decision to start Bouaddi, Fernandez and Anderson together against Brighton.
"I expected a physical game - analysing, watching them, they're aggressive, man-to-man. I watched games they've played, so I think it was a good idea to start with three physical midfielders," the Manchester City manager said.
"And also we were thinking about the last 20 minutes, half an hour to refresh a little bit with Rayan [Cherki] in that case, or Phil [Foden], or Allan. But again, I think in this moment, it's like this. We need just to move on."
Maresca was also asked about the balance of his midfield in a post-match interview with BBC Sport . "We have so many good players, I'm very lucky that I can try different things, and today I think all of them were good," the Italian added.
Rayan Cherki replaced Bouaddi in the second-half and created chances for Fernandez and Matheus Nunes, whilst Nico O'Reilly came on for Fernandez in the closing stages and Phil Foden and Allan Elias were also introduced from the bench.
Iliman Ndiaye saw a fierce strike kept out by Bart Verbruggen with the help of the post shortly after the restart, before O'Reilly headed against the woodwork from the rebound after Ndiaye failed to convert at the back post.
Brighton kept their sixth clean sheet of the season, the most of any side in the Premier League, with Dunk blocking the efforts that Erling Haaland managed to get away during a frustrating afternoon for the Norway international in front of goal.
Anderson revealed afterwards that Maresca told the dressing room the squad wins and loses together , with the England international insisting that Manchester City had created enough chances to win before conceding so early in the match.
Bouaddi arrived from Lille for £86 million in the final weeks of the summer window, and Maresca had said after his first Premier League start against Ipswich Town that the teenager needs a path rather than pressure to start every game.
Fernandez and Anderson, who cost a combined £241 million, had been Maresca's preferred pairing in the biggest games, with Anderson among the five players given three days off before returning to the starting line-up against Brighton.
Nunes and Ndiaye both started at the Etihad Stadium after missing the cup tie in midweek, with Maresca having confirmed on Friday that every player apart from the injured Antoine Semenyo was available for selection.
The defeat was Manchester City's third in six games across all competitions, and it leaves the Blues top of the table on goal difference, with Hürzeler's side now just two points behind in the table and Arsenal able to go three points clear by beating Liverpool on Sunday.
Manchester City travel to face RB Leipzig at the Red Bull Arena in the Champions League on Wednesday night, before a Premier League trip to face Anderson's former club Nottingham Forest at the City Ground next weekend.
