The Hammers defender limped off after half an hour with an ankle injury, following a challenge by Brentford’s Christian Norgaard.
Zouma, 27, was sent for a scan on Monday, ahead of Thursday’s crucial Europa League quarter-final, second leg, against Lyon on Thursday.
West Ham are level in the tie at 1-1 but will already be without left-back Aaron Cresswell following his controversial red card at the London Stadium last Thursday.
“Kurt has twisted his ankle,” said manager David Moyes. “We don’t know how bad it is.
“We’ll get him checked. Coming off is not a good sign but hopefully it’s not too bad.”
The Hammers were on the back foot from the off against the Bees, with Moyes conceding that the taxing Europa League schedule was taking its toll on his thin squad.
“Maybe Thursday-Sunday caught up with us a little bit today,” said the Scot. “We lacked the intensity we’ve got in our general performances. We hardly made any chances.”
West Ham switched off in allowing Bryan Mbuemo to open the scoring from a throw-in routine minutes into the second half, before leaving the Bees forward free to tee up Ivan Toney to double the lead soon after.
West Ham were at least able to welcome back Vladimir Coufal for his first start since undergoing surgery for a hernia earlier this season.
The Czech full-back has revealed he had been battling the injury since last summer’s European Championship.
“I was struggling since the start of the season,” Coufal told Standard Sport.
“It started in the Euros but I didn’t pay attention because I thought it would pass. After it was more serious and more serious and I was still playing.
“I worked really hard for six weeks.
“The first prediction was to return after six weeks. After five weeks I was ready to play. Professor Ernest Schilders did an amazing job with the surgery. Rich and George looked after me and did an amazing job. I need to thank them because they looked after me like their kids.”
After Arsenal and Manchester United lost on Saturday, West Ham missed chance to take advantage in the race for Europe, but Coufal insists they won’t give up their fight.
“Top four is more of a dream than a goal,” said Coufal.
“Our real goal should be top six or to get into Europe next season, whichever way we can do that. It doesn’t matter how we reach it but our goal is to reach European football. [The Brentford defeat] doesn’t change our confidence.
“We have a good squad, a very strong squad. We just maybe need some changes, we will see. I am not the manager so it is up to him. We are going to do everything to bring a semi-final to London Stadium.”