Julian Johnsson will also be out as he is ill. The Faroe Islands midfielder picked up a bug during the week and will be replaced by either Richard Sneekes or Theo Whitmore.
Justin Whittle is still out with a hamstring injury and Nicky Mohan will continue to deputise. Ian Goodison is also missing again. Jason Van Blerk will be in the squad for the first time at Boothferry Park since signing at the start of the year.
Ben Petty is set to be recalled in place of Edwards. Petty hasn't even made the subs bench in the last two games after having a terrible game against Carlisle.
Rodney Rowe will be given a chance in attack, partnering Lawrie Dudfield. New signing Neil Roberts is expected to start the game on the bench but is likely to feature at some stage.
"He's a good player and he's always done well for me. He knows the situation but he's the type of player who will respond very positively to a challenge. I know he won't let us down."
Little continued: "Throughout a season, you will have spells when you will miss key players. Irrespective of who is available, we'll send out what we believe is the best team to win a game.
"We will give it our best and if we do win, we'll try and take something on from there. We couldn't manage that earlier this week but there are still 18 games left this season."
Expected line-up (4-4-2): Musselwhite; Petty, Mohan, Wicks, Holt; Williams, Sneekes, Greaves, Beresford; Rowe, Dudfield.
Subs: Glennon, Van Blerk, Matthews, Whitmore, Roberts.