Ballon d'Or favourite Dembele replaced the injured Doue at the start of the second half on Friday evening, only to suffer a hamstring injury with 10 minutes left of France's World Cup qualifier.
It was a frustrating watch for PSG, who confirmed in a statement the extent of the injuries.
"After leaving the pitch injured during the match between Ukraine and France on Friday, Ousmane Dembele has suffered a serious injury to his right hamstring. He is expected to be unavailable for around six weeks," the European champions said in a medical update.
"Also picking up an injury during the encounter, Desire Doue suffered a strain in his right calf and will be out for around four weeks."
That means both players will miss the first game of PSG's Champions League title defence.
They host Ivan Juric's Atalanta on September 17 and visit Barcelona, Dembele's former club and semi-finalists in 2024/25, on October 1.
Dembele and Doue were outstanding as PSG emphatically won last season's Champions League, with the former solidifying himself as the favourite for the Ballon d'Or with his performances in Europe.
He has strong competition from Spain and Barcelona wonderkid Lamine Yamal, but PSG's Treble win makes him the strong favourite.
Dembele's injury means he will definitely miss three Ligue 1 games and the two aforementioned matches in the Champions League, while it'll be touch-and-go for another two fixtures.
Doue should return to full fitness during next month's international break and be fit to face Strasbourg on October 17.
Their absence should allow Bradley Barcola and Goncalo Ramos to impress Luis Enrique.
Barcola was linked with Liverpool and Bayern Munich in the transfer window, but Fabrizio Romano confirmed in August that PSG want to offer him a new contract.
He wrote on X: "Liverpool consider Bradley Barcola as world class player but no bid or talks at this stage, focus remains on Isak now.
"PSG want to keep Barcola and offer him new deal. Al Khelaifi, Luis Campos who signed him and Luis Enrique are all aligned."
Manchester City have completed a major goalkeeping reshuffle, with long-serving stopper Ederson departing for Fenerbahce and Italy international Gianluigi Donnarumma arriving from Paris Saint-Germain.
Tottenham have strengthened their attacking options with the signing of France international Randal Kolo Muani on a season-long loan from Paris Saint-Germain.
The UEFA Champions League is Europe's most prestigious club football competition, featuring top teams from across the continent.
Bayer Leverkusen have confirmed the signing of AS Monaco midfielder Eliesse Ben Seghir in a deal worth around 35 million euros.
