Dembele faces six weeks out with a hamstring injury, and Doue around four weeks due to a calf problem sustained playing for France.
The 2024/25 treble winners have started the domestic campaign strongly and are unbeaten in Ligue 1. They beat Lens 2-0 on Sunday thanks to a double from 23-year-old France forward Bradley Barcola.
Defender Lucas Beraldo will also miss the Atalanta game on Wednesday due to an ankle problem.
"We have more confidence than last year at this moment of the Champions League," Spaniard Luis Enrique told reporters on Tuesday.
Three defeats and a draw in last season's eight-game league phase left the Parisians outside the top eight, and they reached the knockout rounds only through the playoffs.
"Last year, it was a complicated moment because of the lack of efficiency (due to the number of games). But it is the normal process of a team that wanted to improve... For me, it's harder to win the first than the second or third." Luis Enrique said.
"The first title is always difficult because the players don't think they're capable of winning it. But we showed the way. Now, the whole of PSG and the young players want to win it they know they're capable."
PSG, who stormed to their first Champions League title with a 5-0 victory over Inter Milan in the final, also reached the Club World Cup final in July, where they were beaten 3-0 by Chelsea.
"It is in my mentality to seek improvement, to show the players that there is no calm, or complacency about the future, we must constantly think about getting better," the coach said.
"Our objective is to make history again and to win a second consecutive Champions League and we have to be ambitious."
Atalanta head into Europe under new coach Ivan Juric, who will be managing a Champions League game for the first time.
"They changed their coach so it is tough for us to predict how they will play, but just like in previous seasons, we're talking about a tough team with quality players," Luis Enrique said.
"Gian Piero Gasperini (previous manager) has left his mark on the team, it will be a very demanding match for us."
Gasperini guided Atalanta to their first Europa League title in 2024 and to third place in Serie A last season.