Iniesta and Busquets, sidelined by calf and ankle problems respectively, were both absent from Barca's 1-1 draw at Real Betis last time out.
A tougher challenge awaits on Wednesday, when Luis Enrique takes his team to Vicente Calderon for the first leg of the Copa semi-final.
Asked about the absent captain and his fellow midfield star, the coach insisted the players at his disposal will be sufficient to earn a positive result.
"I'm happy with what I have, with my team," he said.
"We've overcome a lot of difficult moments. We've had injuries. Some have been more important than others.
"But it's not the time to talk about who we don't have. We have to try and help the ones that we do have to play as well as they can.
"If we talk about the players that aren't here - I don't think this is the right time to talk about that."
Rafinha has recovered from a hamstring injury and will travel with the squad to Madrid, together with third-choice goalkeeper Jordi Masip, as number one Marc-Andre ter Stegen is rested. Lucas Digne has been ruled out due to a knee injury.
One player who may be involved is Samuel Umtiti, who has impressed since joining Barca from Lyon in the off-season.
The France international centre-back came in for special praise from Luis Enrique for coping with the burden of expectation that accompanies a switch to one of the world's biggest clubs.
"He's adapted well because of his technical and tactical qualities, not just his physical attributes," he said.
"In looking at his performance - it's only something you can find out when you come to play for Barca. In overcoming different situations on the field and the things that he's done. You can only see when he's here.
"I think you get players from time to time and you think they're going to turn out and play well because they did well at their previous teams. But they come to Barcelona and Real Madrid with extra pressure, [their] performance gets diluted and it becomes more difficult for them to do well.
"But in Umtiti's case it's not just what we expected, he's [also] improving."