Real Madrid beat Alaves 3-2 on Tuesday to move up to second in LaLiga and had five days to prepare for the derby. Atletico travel to Celta Vigo looking to reduce the five-point gap to Real.
Simeone said central midfielder Koke did not train on Wednesday having played more minutes than any other player in the squad.
"We are trying to manage it in the best way possible. We have not changed much, trying to make the training sessions based on the players' workloads so that they arrive at the match in the best possible way," Simeone told reporters.
Packed schedules have been an ongoing concern in European football, especially with a recent run of injuries to high-profile players, including Real Madrid striker Kylian Mbappe and Manchester City midfielder Rodri.
"They are the ones who manage everything, all the rest of us are there to accompany (them), to try to manage. But the only ones who can create change are the footballers, because they are the ones who play," Simeone said.
Simeone backed his strikers Alexander Sorloth and Julian Alvarez to come good with both new recruits having scored only one goal each this season.
"I have no doubt that with time and the partnerships that we will create, they will perform better. It is our job to make them feel better and it is their job to transmit to us those partnerships that are generated in football," Simeone said.
Atleti are fourth in the standings with 12 points after six games while Celta are ninth on nine points.
