Marcus Rashford was tasked with leading Manchester United's attack at Stamford Bridge, while Timo Werner dropped to the Chelsea bench.
Ole Gunnar Solskjaer declared on Friday that he was unsure if Cavani, who has had a positive impact this season since arriving on a free transfer from Paris Saint-Germain, would overcome a knock which has kept him out since mid-February.
Paul Pogba was a confirmed absentee, however, and neither player featured as Solskjaer made five changes to his United team.
Rashford, who has been involved in seven goals in all competitions against Chelsea (five goals, two assists) – more than against any other side in his career – was instead given the central role that Anthony Martial had started in against Real Sociedad on Thursday.
That was one of five changes made by Solskjaer, who also brought back Luke Shaw, Harry Maguire, Scott McTominay and David de Gea.
United are unbeaten in 19 Premier League away games (W13 D6), a run that began with a 2-0 win at Chelsea in February 2020.
This is the Red Devils' longest unbeaten away run in their top-flight history, though their previous longest of 17 between December 1998-September 1999 ended with a 5-0 defeat at Stamford Bridge, and Thomas Tuchel's Chelsea team have been in strong form.
After a frustrating draw with Southampton last week, Chelsea beat Atletico Madrid in the Champions League thanks to Olivier Giroud's stunning winner.
Giroud is rewarded with a start up top, with Tuchel making three alterations.
One of the players to drop out is Werner, who ended his long goalscoring drought in Chelsea's last home game – a 2-0 victory over Newcastle United.
Hakim Ziyech is in to partner Mason Mount – who has scored two goals in his last three Premier League games, as many as in his previous 21 in the competition – behind Giroud, with N'Golo Kante replacing Jorginho in midfield and Ben Chilwell coming in at left wing-back.
Opposite Chilwell, Callum Hudson-Odoi retains his place, despite the youngster being subbed on and subbed off in the draw with Southampton.
The away team has won all four of the previous managerial matches between Tuchel and Solskjaer, with all of those games taking place between United and PSG in the Champions League.