Chris Brunt, James Morrison, Callum McManaman and Jonny Evans will all miss West Brom’s visit of Manchester United on Sunday.
Northern Ireland international star Brunt was added to the injury list after he suffered season-ending cruciate knee ligament damage against Crystal Palace last Saturday.
In addition to the 31-year-old missing the rest of the season, he has also had his dream of playing for his country at Euro 2016 in France this summer shattered by the injury.
Boss Tony Pulis said: “It’s so, so unfortunate for the lad, so, so disappointing. But it’s happened and Chris is going to have to get on with it. What we’re talking about now is making sure we give him as much help as we possibly can to get himself fit for next season.
“This season obviously now has been washed away, the Euros have been washed away. It’s important he focuses on getting himself fully prepared and ready to go for next season.”
Meanwhile, former United defender Evans, McManaman and Morrison remain out with respective hamstring, ankle and hamstring injuries.
Louis van Gaal’s side have had an upturn in results of late but the Baggies have also been buoyed by a run of just two defeats in 10, while they are also unbeaten at home since before Christmas.
“We will go out there and do our best; that’s what we’ve done in all the games,” Pulis added of his approach to facing United.
“They’re a good side, they’ve got some good players. We know it will be a tough game, they’ve had a great result again on Wednesday night so they’ll come full of confidence.
“It’s just making sure the players enjoy the challenge. The big thing is to enjoy it. The last three league games, we’ve won at Everton, we’ve beaten (Crystal) Palace and then we’ve had a good draw at Leicester.
“The last two games, Leicester and Palace, have been full of goals as well so it keeps everybody quiet.”