The veteran striker is tied to City until 2021.
Guardiola said, “It will be one of the toughest challenges. Sergio is irreplaceable.
“We have another incredible striker in Gabriel Jesus and maybe another one will come when Sergio leaves but he is irreplaceable.
“The most important moment of this club – more important than when this club hopefully wins the Champions League – is when Sergio scored that goal against QPR to win the club's first league title for so many years.
“That moment is much better than four titles in one season or whatever – and he was the guy.
“Sooner or later it will happen, he'll decide when he leaves. I'm sure the club will be ready to try to find the guy to replace him but, of course, it will not be easy."