A winner of the 2010 World Cup and Euro 2012, Busquets has earned 118 caps for La Roja since making his debut in 2009.
He remains a key figure at the heart of midfield for club and country and captained the side that drew 0-0 with Portugal in Lisbon on Tuesday.
However, Busquets will be a month short of his 33rd birthday when the postponed Euro 2020 finals begin next June and his starting spot with Spain is already under pressure from Manchester City midfielder Rodri.
Luis Enrique cannot guarantee Busquets will be part of his plans next year if he is not able to sustain his performance levels.
"If he maintains the level of the last 11 years, he'll be at the Euros. If he lowers it, we'll see," said the Spain boss.
"He's a veteran and he's the first to know how this goes. In the end, there comes a time when age counts for everything.
"It's the rule of life. Nobody spends 28 years in the national team."
One player who has forced his way into Luis Enrique's plans is Wolves winger Adama Traore, who made his debut off the bench against Portugal.
The winger's speed, trickery and imposing physique make him a weapon unlike any other at Spain's disposal in attack, and his head coach is delighted to see him flourishing.
He also confirmed Traore's upper-body size is from genetics and general conditioning, not from hours of heavy lifting.
"His case his special. He doesn't lift weights – it's true what he says," the former Barca boss said.
"He's a footballer who doesn't only have speed and an enviable physical structure. It's skill, it's power, it's strength, it's the capacity to hold onto the ball.
"He's a very sensible and thorough person. I'm really glad he's doing well.
"There's no single tactic for a player. There are tactics that try to promote individual qualities from a collective vision.
"A profile like Adama's is unusual. Those qualities are hard to find at this level and we'll try to integrate him into our team."
Spain play their third game of Nations League Group A4 on Saturday against Switzerland at Real Madrid's Estadio Alfredo Di Stefano.
The match is due to go ahead despite Madrid having been put back into a state of alarm as a result of rising coronavirus cases over the past two months.
"The players can't be worried," Luis Enrique said. "We'd like the news to be otherwise, to be able to play with fans [attending].
"We're living in a bubble, with tests every few days, without contact with people from outside... there's a general wish that this can be resolved as soon as possible."