Cavani was absent from the matchday squad as United and Chelsea played out a dour draw on Sunday, neither team hitting a 1.0 xG during the 90 minutes.
Cavani has been out since the 1-1 draw at West Brom and posted on Sunday evening on Instagram that he was "eager to come back soon” - and starts at Selhurst Park.
However, De Gea misses out on the squad altogether, with Lee Grant on the bench as Dean Henderson starts in goal.
Anthony Martial was named on the bench at Stamford Bridge, coming on for the final 10 minutes, but misses out again here.
Elsewhere, Paul Pogba, Juan Mata and Phil Jones are injured. Pogba has been ruled out since sustaining a thigh complaint against Everton on February 6.
Jones has not played this season due to a knee injury, having last featured for United in the FA Cup fourth-round win at Tranmere in January 2020.
Asked if the England defender could play at all this season, Solskjaer said: "With Phil, obviously we hope so but he's working really hard.
"He's had a couple of setbacks and it's just that kind of injury that you have to be patient and give him time. I know all about knee injuries.
"I'm not sure (when he will be back). How long is a piece of rope? That's how I felt as well when I came back. So (we'll) give him absolutely every chance to get back this season. If not, hopefully for the start of next."
Man Utd lineup: Henderson, Wan Bissaka, Bailly, Maguire, Shaw, Fred, Matic, Greenwood, Bruno Fernandes, Rashford, Cavani
Subs: Lindelof, Grant, Diallo, James, Alex Telles, Williams, Tuanzebe, McTominay, Shoretire
Injury list: Pogba, Mata, Jones, Mejbri, De Gea
Wednesday 8.15pm, Sky Sports
Venue: Selhurst Park
Referee: Andre Marriner