Michael Carrick, Marcos Rojo, Phil Jones and Daley Blind have all been ruled out of the game at Stamford Bridge in London.
"It's part of life in football," the boss says. Hear more from Louis van Gaal on #MUTV from 12:00 BST.— Manchester United (@ManUtd) April 17, 2015
This will come as a huge blow to United, who have recently put together a run of positive results and are in contention of finishing second in the Premier League this season.
Midfielder Carrick has been one of the unsung heroes for the Red Devils, while Jones and Blind are key members of a strong United back-line.
Defensively United looked vulnerable in the opening months of the season, but they have become better in that department in recent times and the absence of the key players in that area could cost them dear against Chelsea.
United will head into tomorrow’s encounter placed third in the Premier League table with 65 points from 32 matches.
Meanwhile, Jose Mourinho’s Chelsea currently find themselves seven points clear at the top of the standings with a game in hand.