The Ireland international is undergoing a rehabilitation programme following knee surgery and is not expected to resume training for another three to four months.
O'Brien, 20, has not featured for Bolton in the current campaign after suffering the setback in pre-season.
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Sam Allardyce initially thought the defender would be available for part of the festive programme but those hopes have been dashed.
The Bolton boss said: 'Joey is really distraught. When he finished here last year he was on a high after playing 28-30 games.
'Then before the season got under way, he was stricken by an injury that has become increasingly worrying.
'He has experienced the accolades, now he is experiencing the cruelty of the game.
'Joey is on a rehabilitation programme and is going to be out for another three to four months.
'As he has had surgery we have to make sure we get this injury 100% right for his long-term future. It should stand the lad in real good stead.'