The midfielder had picked up an injury on international duty with Belgium last weekend.

He was substituted in the second half of Belgium’s 2-1 UEFA Nations League defeat by England at Wembley last Sunday and then withdrew from the squad with an unspecified injury.

“The squad has come back a little better than the previous time. Unfortunately, Kevin is out. But the rest of the players came back well,” Guardiola told reporters.

“I don’t think it’s much. But the next games, I think, he will be out,” added the Spaniard, on the extent of De Bruyne’s injury.

“But we will see day by day how he is going on.”

Manchester City have a busy fixture list, hosting Porto in the UEFA Champions League group stage on Wednesday before a league trip to West Ham on the following Saturday.

They then travel to Marseille for another group stage game the Tuesday after.

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In the game which had Real Madrid captain Sergio Ramos sent off, Kevin De Bruyne kept his cool to beat Belgium team mate Thibaut Courtois from the penalty kick spot.

His goal in the 82nd minute gave Manchester City the lead, after Gabriel Jesus had headed home a cross from De Bruyne to pull the visitors level in the 78th minute.

Isco had given Real Madrid the lead on the hour mark following a sweeping counter-attack, but the 13-times European champions’ night soon unraveled.

It culminated in Ramos being sent off for hauling down Jesus in a bid to prevent a third Manchester City goal.

Ramos will be suspended for the second leg at the Etihad Stadium on March 17.

Manchester City’s influential defender Aymeric Laporte was forced off injured in the first half, another setback in a season marked by fitness troubles.

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Roberto Martinez’s side, top of the FIFA rankings, were a class above their hosts as they scored three times before halftime through Romelu Lukaku, Thomas Vermaelen and Toby Alderweireld — all created by Kevin de Bruyne.

De Bruyne then capped a superb individual display with a clinical finish late on.

Victory left Belgium with 18 points from six games, three more than second-placed Russia who needed an 89th-minute goal by Mario Fernandes to beat Kazakhstan 1-0.

The top two go through to next year’s finals.

Scotland’s joint heaviest home defeat means their slender hopes of qualifying from the group are virtually over, although they could still reach the tournament via the Nations League playoffs, with a semi-final place already secured.

Belgium needed only nine minutes to take the lead with their first serious foray into Scottish territory.

Moments after Scotland had a free kick at the other end, Belgium counter-attacked in deadly fashion with Dries Mertens driving forward before finding De Bruyne who rolled a pass across the pitch for Lukaku to score with ease.

It completely knocked the stuffing out of the Scots and it was 2-0 in the 24th minute when De Bruyne whipped in a cross and Vermaelen arrived to side-foot past keeper David Marshall.

The game was effectively over already and Scotland’s night got even worse in the 32nd minute when De Bruyne swung over a corner and an unmarked Alderweireld headed in off the crossbar.

It was a passion-less display by Scotland and Belgium could afford the luxury of playing the rest of the match in cruise control as they claimed another easy three points.

De Bruyne saved the best goal to last as he planted a first-time shot past Marshall after being played in by Lukaku.

Scotland dropped to second from bottom in the table after Cyprus beat San Marino 4-0 to move above the Scots by a point.

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