City meet Liverpool on Sunday having been knocked out in their Champions League round 16 playoff against Real Madrid.
City sit in fourth place facing Premier League leaders Liverpool and Guardiola admits the situation does require a squad change.
"We have to sit down with the doctors, the players, agents and be clear that some of them cannot sustain playing every three days," Guardiola said.
"This is the reality. A lot of players cannot sustain what we have done in the past every week in, week out. Playing in different competitions, travel without the problems. You tell me where my concern is? Just that.
"We deserve to have a bad season, it can happen. The reality is for the future if we want to be there again, in the latter stages of the Champions League, we need players fit and available. Of course I am concerned.
'It can happen sometimes but already it happens many times. It's so, so demanding - the teams are quicker, faster, stronger and we cannot handle it right now. I remember before the first leg against Madrid we had all central defenders back and I said, 'guys, now you will see'. One week later, two central defenders out for months. The season has been like that."