The 22-year-old Frenchman was brought in for £6million from Olympiacos in August as cover for injured left-back Aaron CresswellBut Masuaku has now joined Cresswell on the casualty list after damaging knee ligaments during the EFL Cup win over Accrington on Wednesday night.
For manager Slaven Bilic it is another problem to solve in a defence which conceded eight goals in their previous two Premier League outings.
The Hammers face Southampton on Sunday without a recognised senior left-back, so one of Alvaro Arbeloa or Sam Byram will have to move across from right-back to fill in.
“Masuaku did his knee against Accrington, he damaged ligaments and we will know better in a week but it’s going to be at least six weeks, if not more,” said Bilic.
“Some players can play in different positions, and you can fill gaps, but when you have two left-backs who have done the same ligaments it’s not good news.
“But I’m not looking for excuses. But we have a good team and I expect us to do it on Sunday.”
Bilic can welcome centre-half Winston Reid back after a couple of weeks on the sidelines and also had positive news on Cresswell, as well as injury-hit striker Andy Carroll.
“It was in the papers on the day we played Accrington that Carroll had had a setback, but it’s not true,” he added.
“We are expecting him and Cresswell to join and train with the team after the international break.
“Injury wise we look much better than at the beginning of the season. We have a good team and I expect us to be really good in every way on Sunday afternoon.”
Summer signing Andre Ayew and fellow forward Diafra Sakho are still out injured.
The visit of Saints is the first Premier League match at the London Stadium since trouble flared among fans during the 4-2 defeat by Watford.
The West Ham board are attempting to solve the problems by improving stewarding, relocating disgruntled fans and beefing up the segregation between rival supporters.
Defeat on Sunday could see West Ham slump to the foot of the table so Bilic has urged the fans to put the off-field issues to one side and back the team.
“I want the fans to be behind us, and they will be,” he said.
“We need their support more than ever and they will play a big part in this game. We need them all the time, but especially now to help get out of this situation. I have no doubt they will be very positive.”
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