According to reports from The Athletic journalists Simon Johnson and Mario Cortegana, James is expected to be sidelined for several weeks with a hamstring injury, leaving him doubtful for the clash against Manchester City, which is now less than a month away.
Chalobah's situation is also uncertain after he suffered a serious-looking ankle injury during a match against Paris Saint-Germain. The centre-back was stretchered off after his ankle twisted awkwardly in a challenge, later posting on social media that it "should be broken".
However, manager Liam Rosenior remains hopeful the damage is limited to a sprain, though a high-ankle injury could still rule him out for up to six weeks.
"I think he was really worried," Rosenior said of Chalobah. "I've just checked with the medical team. We'll obviously scan and assess him tomorrow. We are hoping and praying that it's not as bad as we first feared.
"He's got a high ankle sprain, so I'm praying it's nothing too serious because we can't lose another defender."
On James, he added: "I'm waiting for the full results of his scan. Hopefully he is back sooner rather than later."
The timing is far from ideal for Chelsea, with the fixture widely viewed as one of City's toughest remaining matches in the title run-in.
League leaders Arsenal currently hold a nine-point advantage, but with City holding a game in hand - and a looming showdown between the two sides - the gap could quickly shrink.