Josh Coulson is set to miss “several weeks” of action with a hamstring injury.
The 29-year-old picked up the injury in last weekend’s 3-0 home defeat to Salford City.
Coulson has played an instrumental part in the club’s season, having started every league game, which sees the O’s top of the National League.
Orient confirmed the centre-back’s injury ahead of their trip to promotion rivals Wrexham in the FA Trophy second round.
Justin Edinburgh’s side then play at Ebbsfleet United in the National League before returning to Brisbane Road for the visit of Maidstone United.