Aguero, City's leading scorer, has missed their past four matches with a groin problem but has been able to train without discomfort and could face Everton at the Etihad Stadium on Saturday.
Belgium midfielder De Bruyne suffered ligament damage to his right knee in August and although he returned in October, he then injured his left knee during the League Cup win over Fulham on November 1.
He too has resumed full training and Guardiola will assess both players in the hope that his lengthy casualty list might be about to ease.
The City boss said he was down to 15 fit senior players for Wednesday’s 2-1 Champions League victory over Hoffenheim, and remains without a significant chunk of his squad.
Playmaker David Silva, full-back Benjamin Mendy and goalkeeper Claudio Bravo are longer-term absentees, while defenders John Stones and Danilo, plus midfielder Fernandinho, will have late fitness checks before Guardiola makes a decision on whether to include them.
The manager, though, is optimistic on 30-year-old Aguero, who has 12 goals in all competitions this season.
"He did the last two training sessions, including on Thursday and he has no pain in his injury so we'll decide," he said.
"Kevin is in the same situation as Sergio. Yesterday he trained with no pain, we will see."
The win over Hoffenheim enabled City to get back on track after the disappointment of seeing their 15-match unbeaten start to the Premier League season end in a 2-0 defeat at Chelsea last Saturday.
With Liverpool not playing until Sunday, when they host Manchester United, City will go back to the top, at least for a day, if they avoid defeat against Marco Silva's side.
Everton were one of only three visiting league teams to avoid defeat at the Etihad Stadium last season, and Guardiola is wary of opponents who start the weekend sitting seventh in the Premier League.
The manager also wants his players to step up their form going into the Christmas programme in order to bring some extra cheer to supporters.
"Last season, when we dropped points, we were able to respond with another big run," he said.
“We must focus on what we have to do. Christmas is here, people are on holidays, the families are back together, enjoying their Christmas. For us, it's the toughest time of the season and it's time to be focused."
Guardiola has been impressed by how difficult to beat Everton have become under Silva's management.
They have lost just one of their past six Premier League matches, drawing at Chelsea during that run.
Their only defeat in that sequence came at neighbours Liverpool, when they conceded a freakish injury-time goal to Divock Origi.
"Everton have quality up front," he said. "Richarlison did so well with Watford, then when Marco came here he brought him. He's a top player, and that’s why they paid a lot.
"They did not just play well at Liverpool, they did so at Chelsea too. Marco's teams are always well organised. We need to attack them better, move freely and hopefully the quality of our players makes a difference."AFP