Midfielders Danny Sonner (achilles) and Neil Roberts, (ankle) and centre-back Steve Evans, all missed the 1-1 draw against Mansfield Town on Saturday.
Little is hopeful that Sonner, a late withdrawal at the weekend after suffering a reaction to the problem which saw him miss the previous match against Peterborough, is passed fit for the derby clash, but he admitted time might be against Roberts and Evans.
"We were missing three or four players against Mansfield on Saturday and that is about 30 per cent of a team," said Little. "That's a big chunk, and Danny, Neil and Steve have all done very well in our recent good run.
"We prepared for Danny in the run up to the game and he trained on Friday, but I had a call on Saturday morning to say his achilles had flared up again and was sore.
"You can't play with that problem and it was disappointing. I just hope Danny is okay for Sunday and we'll monitor him after a few days rest.
"We will assess Neil and Steve this week. We have to make sure they are right but at the moment I would say they are both doubtful, Neil more so than Steve.
"Sunday might come too early for them but we'll have to wait and see."
Having seen Wrexham battle back to draw against Mansfield, Little stressed the importance of scoring the opening goal to clinch victories in the battle to avoid relegation.
"If we had scored first we would have been more disappointed with the draw," added Little.
"We defended well enough but it always looked like one goal might settle it. We went behind, and it took a massive deflection, but dug in to get back into it.
"We can't go out expecting to play teams off the park at the moment.
"Against Milton Keynes Dons and Darlington, we proved that if we can score first we can win.
"The mentality of not losing is very important. Of course we try to win games but that opening goal is so important."
Ask Brian
If you have a question for Brian Little email it to digitalnews@nwn.co.uk and we'll ask as many as we can during our next video interview with the Reds boss this Thursday.
The full article contains 403 words and appears in n/a newspaper.