The midfielder was withdrawn during the first half of last weekend's 1-0 defeat at Brentford with an ankle injury and is unlikely to recover in time to face the O's.
John Mousinho was Welsh's replacement at Griffin Park and is the favourite to start in central midfield while Keith Keane is another alternative.
Bailey Wright (ankle) and Will Hayhurst (hamstring) were both ruled out against the Bees and will face late fitness tests ahead of the game.
Joel Byrom (hernia) and Scott Laird (broken leg) are also on the road to recovery but the match against Russell Slade's men will come too soon for both.
Manager Simon Grayson has so far resisted the temptation to enter the loan market to bolster his squad and is keen to keep faith with his current group of players as they look for a positive end to the campaign.