West Ham winger Michail Antonio has been ruled out for the rest of the season.
Manager Slaven Bilic confirmed the 26-year-old suffered a "significant" hamstring injury against Swansea last weekend.
Antonio, who had just returned to the side following a similar injury, pulled up moments before half-time during West Ham's 1-0 win.
The new problem could also make him a doubt for England's World Cup qualifier against Scotland on June 10.
"It is a significant injury, he is out for the season," said Bilic.
"It's a big blow, he is one of our best players."
Captain Mark Noble begins a two-match ban but Bilic is confident Andy Carroll, Sam Byram and Aaron Cresswell will be fit to face Sunderland on Saturday.
Striker Carroll was an unused sub against the Swans, Byram rolled his ankle during the match and fellow defender Cresswell has missed two games with a muscle problem.
West Ham, who had lost their previous five matches before last weekend's win, head north to meet the bottom side knowing one more victory should end any fears of relegation.
Bilic added: "It's a big game for us, Sunderland are desperate for a win and we are looking to win to secure or get closer to securing safety.
"Every win gives you a boost, especially after five defeats in a row. The confidence is back but the belief was permanent and we never lost it."
Bilic has also had to contend with yet another manager being linked with his job, with Fulham's Slavisa Jokanovic the latest name on the list.
The Croatian said: "I know Slavisa, we are from the same region and speak the same language. I like him as a person and as a manager but I am not bothered.
"I don't talk to the owners about every name that appears in the papers."