Colchester United's John-Joe O'Toole could be out for up to nine months after rupturing a cruciate ligament.
The midfielder, 21, sustained the injury in Tuesday's defeat at Charlton.
Manager Aidy Boothroyd told BBC Essex: "He's really disappointed, but it is part and parcel of football unfortunately, it's a blow for him.
"We've got to make sure when we does come back that we work as hard as we can to ensure he's playing in a different division."
The League One promotion chasers visit Hartlepool United this weekend and could have defender Franck Queudrue back from a hamstring injury.
Striker Kayode Odejayi is set to miss out with a foot injury.
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