McGuire, 30, suffered a break to his fibula and will have an operation later today to plate the break.
It was hoped that he may be able to return to action within eight weeks but further scans have revealed ligament damage, which could see McGuire on the sidelines for up to four months.
Leeds coach Brian McDermott said: “This is a bitter blow for Danny and the team. We had hoped he would be back sooner rather than later but the scans were not good news and it is going to be a lengthy lay off.
“Danny has been in this situation before and I know he will be able to handle it mentally but it is certainly a blow. Our medical team will give him the best possible support and I am sure he will be working hard to get back to full fitness.”