Neymar was absent from the PSG squad amid continued uncertainty over his future at the club and Thomas Tuchel lost striker Cavani 14 minutes into a goalless first half.
Eric Maxim Choupo-Moting came on for the Uruguayan and opened the scoring in the 50th minute with a superb solo strike, before defender Mathieu Goncalves turned in an own goal.
The result was completely overshadowed, though, as Mbappe appeared to pull his hamstring when chasing down a pass, with the France forward heading straight off the pitch before Choupo-Moting and Marquinhos added further goals.
PSG, beaten 2-1 at Rennes last week, quickly cranked into gear and Toulouse goalkeeper Baptiste Reynet made a pair of smart saves from Mbappe in the opening four minutes.
But their strong start faded fast and PSG were dealt a blow when Tuchel saw Cavani hobble off after an attempted volley, with Choupo-Moting introduced as his replacement.
Choupo-Moting was acrobatically denied by Reynet in the first minute after the restart but the keeper could do nothing about the Cameroon international's next effort.
After collecting the ball in a packed penalty box, Choupo-Moting superbly span into space and thumped a low drive in off the left post.
PSG's second goal came five minutes later, Pablo Sarabia's attempt deflecting in off Goncalves, who then gave away a 71st-minute penalty for handball after Mbappe pulled up on his 100th Ligue 1 appearance.
Reynet dived to his right to deny Angel Di Maria from the spot, but PSG added a third goal four minutes later as a sweeping move ended with Juan Bernat teeing up Choupo-Moting for a first-time finish.
Choupo-Moting was denied a hat-trick by Reynet before Marquinhos' header completed the scoring on his 250th appearance for the club, but PSG will be hoping for good news on Cavani and Mbappe.
What does it mean? Injury issues mount for PSG
The European transfer window closes on September 2 and it remains unclear whether Neymar will stay at PSG, but the issues for Cavani and Mbappe could force the club to keep him.
Losing one striker to injury would be unfortunate but two was a horrible stroke of bad luck that will likely leave PSG increasingly reliant on Choupo-Moting in the coming weeks.
Choupo-Moting makes his case
Eyebrows were raised when PSG signed Choupo-Moting on a free transfer last year, the forward having been released by Stoke City. He scored only three times in 22 Ligue 1 games last term.
But perhaps the 2019-20 season will be the making of the 30-year-old. Choupo-Moting took his goals very well indeed and if Mbappe and Cavani are out for an extended time he will get more chances to shine.
Nightmare debut for Goncalves
Toulouse coach Alain Casanova threw Goncalves to the wolves somewhat by asking the 18-year-old to make his debut against the Ligue 1 champions and the teenager crumbled under the pressure, scoring an own goal and giving away a penalty before being replaced by Wesley Said.
PSG return to action on Friday, taking on Metz in their last game before the international break. Toulouse are at home to Amiens a day later.