The experienced defender lasted just over an hour during the Hammers’ midweek win at the Boleyn Ground before pulling up with hamstring problem and later being replaced by teenager Reece Oxford.
With Winston Reid suffering from a long-term injury, Collins’ lay-off is a blow for West Ham and boss Bilic foresees the Wales international missing the next three matches.
"James got injured on Wednesday and that is a big blow because he has been marvellous. It's not one week or a few days, but it looks like he will miss three games,” the Croatian boss told the London Evening Standard.
Reid’s injury has allowed Collins to regain a spot in West Ham’s starting lineup, and he hasn’t put a foot wrong in recent weeks, impressing both supporters and pundits alike.
With the European Championships on the horizon and Collins initially struggling for first-team action, he was tipped to leave in January but the decision to stay has since turned out well for both club and player.
West Ham travel to Everton this weekend looking to keep up their good run of form and make a late push for a Champions League spot ahead of an out-of-form Manchester City.
Collins’ absence could prove problematic in their quest, although they held on comfortably enough against Spurs and Bilic will be keen for his side to maintain their defensive solidarity in the upcoming weeks.